Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function
Cumulative evidence suggests the importance of organelle homeostasis in regulating metabolic functions in response to various cellular stresses. Particularly, the dynamism and health of the mitochondria-peroxisome network through fission and fusion are essential for cellular function; dysfunctional...
Gespeichert in:
| Veröffentlicht in: | Journal of molecular medicine (Berlin, Germany) Germany), 2016-12, Vol.94 (12), p.1373-1384 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1384 |
|---|---|
| container_issue | 12 |
| container_start_page | 1373 |
| container_title | Journal of molecular medicine (Berlin, Germany) |
| container_volume | 94 |
| creator | Kim, Dongkyun Song, Jinsoo Kang, Yeonho Park, Sujung Kim, Yong-Il Kwak, Seongae Lim, Dongkwon Park, Raekil Chun, Churl-Hong Choe, Seong-Kyu Jin, Eun-Jung |
| description | Cumulative evidence suggests the importance of organelle homeostasis in regulating metabolic functions in response to various cellular stresses. Particularly, the dynamism and health of the mitochondria-peroxisome network through fission and fusion are essential for cellular function; dysfunctional dynamism underlies the pathogenesis of several degenerative diseases including Parkinson’s disease. Here, we investigated the role of Fis1 in cartilage homeostasis and its relevance to osteoarthritis (OA). We found that Fis1 is significantly suppressed in human OA chondrocytes compared to that in normal chondrocytes. Fis1 depletion through siRNA induced peroxisomal dysfunction. Moreover, Fis1 suppression altered miRNA profiles, especially those implicated in lysosomal regulation. Lysosomal destruction using LAMP-1-specific targeted nanorods or lysosomal dysfunction through chloroquine treatment resulted in enhanced chondrocyte apoptosis and/or suppression of autophagy. Accordingly, lysosomal activity and autophagy were severely decreased in OA chondrocytes despite abundant LAMP-1-positive organelles. Moreover, Fis1 morpholino-injected zebrafish embryos displayed lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction. Collectively, these data suggest interconnected links among Fis1-modulated miRNA, lysosomes, and autophagy, which contributes to chondrocyte survival/apoptosis. This study represents the first functional study of Fis1 with its pathological relevance to OA. Our data suggest a new target for controlling cartilage-degenerative diseases, such as OA.
Key message
Fis1 suppression in OA chondrocytes induces accumulation and inhibition of lysosomes.
Fis1 suppression alters miRNAs, especially those implicated in lysosomal regulation.
Lysosomal destruction results in chondrocyte apoptosis and suppression of autophagy.
Fis1 depletion in zebrafish causes lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction.
This is the first functional study of Fis1 and its pathological relevance to OA. |
| doi_str_mv | 10.1007/s00109-016-1445-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1868331877</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4272022561</sourcerecordid><originalsourceid>FETCH-LOGICAL-c541t-eb3fe60ff145346df2eeeed3c3a3f0acc3fd4434315ebbb8f3dc38a9db4e33b3</originalsourceid><addsrcrecordid>eNqNkVFr3iAUhmW0rN_a_YDdlEBvdpNVo4l6WUq7DQq76b0YPbaWJKaepPT790vItzEKhXkjLz4-B30J-cLoN0apvERKGdUlZU3JhKhL_YHsmODVmugR2VEtmrKSrDkhnxCfFlrWWnwkJ5UUWupa7Yi_jcgKD2MHU0xDEYci4QTJ5ukxxyliEfvRxoyFe0yDz8ntJyhwzi_xxXaFHXwxQk6vEVN_yN0e05bCPLjVekaOg-0QPh_2U3J_e3N__aO8-_X95_XVXelqwaYSWh6goSEwUXPR-FDBsjx33PJArXM8eCG44KyGtm1V4N5xZbVvBXDe8lPyddOOOT3PgJPpIzroOjtAmtEw1SjOmZLyP1AhlVRa6QW9eIM-pTkPyztWqmnWn-QLxTbK5YSYIZgxx97mvWHUrGWZrSyzlGXWssxqPj-Y57YH__fGn3YWoNoAXI6GB8j_jH7X-hu4d6Hg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1846649793</pqid></control><display><type>article</type><title>Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function</title><source>MEDLINE</source><source>SpringerLink</source><creator>Kim, Dongkyun ; Song, Jinsoo ; Kang, Yeonho ; Park, Sujung ; Kim, Yong-Il ; Kwak, Seongae ; Lim, Dongkwon ; Park, Raekil ; Chun, Churl-Hong ; Choe, Seong-Kyu ; Jin, Eun-Jung</creator><creatorcontrib>Kim, Dongkyun ; Song, Jinsoo ; Kang, Yeonho ; Park, Sujung ; Kim, Yong-Il ; Kwak, Seongae ; Lim, Dongkwon ; Park, Raekil ; Chun, Churl-Hong ; Choe, Seong-Kyu ; Jin, Eun-Jung</creatorcontrib><description>Cumulative evidence suggests the importance of organelle homeostasis in regulating metabolic functions in response to various cellular stresses. Particularly, the dynamism and health of the mitochondria-peroxisome network through fission and fusion are essential for cellular function; dysfunctional dynamism underlies the pathogenesis of several degenerative diseases including Parkinson’s disease. Here, we investigated the role of Fis1 in cartilage homeostasis and its relevance to osteoarthritis (OA). We found that Fis1 is significantly suppressed in human OA chondrocytes compared to that in normal chondrocytes. Fis1 depletion through siRNA induced peroxisomal dysfunction. Moreover, Fis1 suppression altered miRNA profiles, especially those implicated in lysosomal regulation. Lysosomal destruction using LAMP-1-specific targeted nanorods or lysosomal dysfunction through chloroquine treatment resulted in enhanced chondrocyte apoptosis and/or suppression of autophagy. Accordingly, lysosomal activity and autophagy were severely decreased in OA chondrocytes despite abundant LAMP-1-positive organelles. Moreover, Fis1 morpholino-injected zebrafish embryos displayed lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction. Collectively, these data suggest interconnected links among Fis1-modulated miRNA, lysosomes, and autophagy, which contributes to chondrocyte survival/apoptosis. This study represents the first functional study of Fis1 with its pathological relevance to OA. Our data suggest a new target for controlling cartilage-degenerative diseases, such as OA.
Key message
Fis1 suppression in OA chondrocytes induces accumulation and inhibition of lysosomes.
Fis1 suppression alters miRNAs, especially those implicated in lysosomal regulation.
Lysosomal destruction results in chondrocyte apoptosis and suppression of autophagy.
Fis1 depletion in zebrafish causes lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction.
This is the first functional study of Fis1 and its pathological relevance to OA.</description><identifier>ISSN: 0946-2716</identifier><identifier>EISSN: 1432-1440</identifier><identifier>DOI: 10.1007/s00109-016-1445-9</identifier><identifier>PMID: 27497958</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Apoptosis - drug effects ; Autophagy - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Cartilage, Articular - drug effects ; Cartilage, Articular - metabolism ; Cartilage, Articular - pathology ; Chloroquine - pharmacology ; Chondrocytes - drug effects ; Chondrocytes - metabolism ; Chondrocytes - pathology ; Danio rerio ; Embryo, Nonmammalian ; Gene Expression Regulation ; Human Genetics ; Humans ; Internal Medicine ; Lysosomal Membrane Proteins - genetics ; Lysosomal Membrane Proteins - metabolism ; Lysosomes - drug effects ; Lysosomes - metabolism ; Membrane Proteins - antagonists & inhibitors ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondrial Proteins - antagonists & inhibitors ; Mitochondrial Proteins - genetics ; Mitochondrial Proteins - metabolism ; Molecular Medicine ; Morpholinos - genetics ; Morpholinos - metabolism ; Original Article ; Osteoarthritis - genetics ; Osteoarthritis - metabolism ; Osteoarthritis - pathology ; Peroxisomes - drug effects ; Peroxisomes - metabolism ; Primary Cell Culture ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Signal Transduction ; Zebrafish - embryology ; Zebrafish - genetics ; Zebrafish - metabolism</subject><ispartof>Journal of molecular medicine (Berlin, Germany), 2016-12, Vol.94 (12), p.1373-1384</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><rights>Journal of Molecular Medicine is a copyright of Springer, 2016.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-eb3fe60ff145346df2eeeed3c3a3f0acc3fd4434315ebbb8f3dc38a9db4e33b3</citedby><cites>FETCH-LOGICAL-c541t-eb3fe60ff145346df2eeeed3c3a3f0acc3fd4434315ebbb8f3dc38a9db4e33b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00109-016-1445-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00109-016-1445-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27497958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Dongkyun</creatorcontrib><creatorcontrib>Song, Jinsoo</creatorcontrib><creatorcontrib>Kang, Yeonho</creatorcontrib><creatorcontrib>Park, Sujung</creatorcontrib><creatorcontrib>Kim, Yong-Il</creatorcontrib><creatorcontrib>Kwak, Seongae</creatorcontrib><creatorcontrib>Lim, Dongkwon</creatorcontrib><creatorcontrib>Park, Raekil</creatorcontrib><creatorcontrib>Chun, Churl-Hong</creatorcontrib><creatorcontrib>Choe, Seong-Kyu</creatorcontrib><creatorcontrib>Jin, Eun-Jung</creatorcontrib><title>Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function</title><title>Journal of molecular medicine (Berlin, Germany)</title><addtitle>J Mol Med</addtitle><addtitle>J Mol Med (Berl)</addtitle><description>Cumulative evidence suggests the importance of organelle homeostasis in regulating metabolic functions in response to various cellular stresses. Particularly, the dynamism and health of the mitochondria-peroxisome network through fission and fusion are essential for cellular function; dysfunctional dynamism underlies the pathogenesis of several degenerative diseases including Parkinson’s disease. Here, we investigated the role of Fis1 in cartilage homeostasis and its relevance to osteoarthritis (OA). We found that Fis1 is significantly suppressed in human OA chondrocytes compared to that in normal chondrocytes. Fis1 depletion through siRNA induced peroxisomal dysfunction. Moreover, Fis1 suppression altered miRNA profiles, especially those implicated in lysosomal regulation. Lysosomal destruction using LAMP-1-specific targeted nanorods or lysosomal dysfunction through chloroquine treatment resulted in enhanced chondrocyte apoptosis and/or suppression of autophagy. Accordingly, lysosomal activity and autophagy were severely decreased in OA chondrocytes despite abundant LAMP-1-positive organelles. Moreover, Fis1 morpholino-injected zebrafish embryos displayed lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction. Collectively, these data suggest interconnected links among Fis1-modulated miRNA, lysosomes, and autophagy, which contributes to chondrocyte survival/apoptosis. This study represents the first functional study of Fis1 with its pathological relevance to OA. Our data suggest a new target for controlling cartilage-degenerative diseases, such as OA.
Key message
Fis1 suppression in OA chondrocytes induces accumulation and inhibition of lysosomes.
Fis1 suppression alters miRNAs, especially those implicated in lysosomal regulation.
Lysosomal destruction results in chondrocyte apoptosis and suppression of autophagy.
Fis1 depletion in zebrafish causes lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction.
This is the first functional study of Fis1 and its pathological relevance to OA.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Autophagy - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cartilage, Articular - drug effects</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cartilage, Articular - pathology</subject><subject>Chloroquine - pharmacology</subject><subject>Chondrocytes - drug effects</subject><subject>Chondrocytes - metabolism</subject><subject>Chondrocytes - pathology</subject><subject>Danio rerio</subject><subject>Embryo, Nonmammalian</subject><subject>Gene Expression Regulation</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Lysosomal Membrane Proteins - genetics</subject><subject>Lysosomal Membrane Proteins - metabolism</subject><subject>Lysosomes - drug effects</subject><subject>Lysosomes - metabolism</subject><subject>Membrane Proteins - antagonists & inhibitors</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondrial Proteins - antagonists & inhibitors</subject><subject>Mitochondrial Proteins - genetics</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Molecular Medicine</subject><subject>Morpholinos - genetics</subject><subject>Morpholinos - metabolism</subject><subject>Original Article</subject><subject>Osteoarthritis - genetics</subject><subject>Osteoarthritis - metabolism</subject><subject>Osteoarthritis - pathology</subject><subject>Peroxisomes - drug effects</subject><subject>Peroxisomes - metabolism</subject><subject>Primary Cell Culture</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Signal Transduction</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish - genetics</subject><subject>Zebrafish - metabolism</subject><issn>0946-2716</issn><issn>1432-1440</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkVFr3iAUhmW0rN_a_YDdlEBvdpNVo4l6WUq7DQq76b0YPbaWJKaepPT790vItzEKhXkjLz4-B30J-cLoN0apvERKGdUlZU3JhKhL_YHsmODVmugR2VEtmrKSrDkhnxCfFlrWWnwkJ5UUWupa7Yi_jcgKD2MHU0xDEYci4QTJ5ukxxyliEfvRxoyFe0yDz8ntJyhwzi_xxXaFHXwxQk6vEVN_yN0e05bCPLjVekaOg-0QPh_2U3J_e3N__aO8-_X95_XVXelqwaYSWh6goSEwUXPR-FDBsjx33PJArXM8eCG44KyGtm1V4N5xZbVvBXDe8lPyddOOOT3PgJPpIzroOjtAmtEw1SjOmZLyP1AhlVRa6QW9eIM-pTkPyztWqmnWn-QLxTbK5YSYIZgxx97mvWHUrGWZrSyzlGXWssxqPj-Y57YH__fGn3YWoNoAXI6GB8j_jH7X-hu4d6Hg</recordid><startdate>20161201</startdate><enddate>20161201</enddate><creator>Kim, Dongkyun</creator><creator>Song, Jinsoo</creator><creator>Kang, Yeonho</creator><creator>Park, Sujung</creator><creator>Kim, Yong-Il</creator><creator>Kwak, Seongae</creator><creator>Lim, Dongkwon</creator><creator>Park, Raekil</creator><creator>Chun, Churl-Hong</creator><creator>Choe, Seong-Kyu</creator><creator>Jin, Eun-Jung</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7QP</scope></search><sort><creationdate>20161201</creationdate><title>Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function</title><author>Kim, Dongkyun ; Song, Jinsoo ; Kang, Yeonho ; Park, Sujung ; Kim, Yong-Il ; Kwak, Seongae ; Lim, Dongkwon ; Park, Raekil ; Chun, Churl-Hong ; Choe, Seong-Kyu ; Jin, Eun-Jung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-eb3fe60ff145346df2eeeed3c3a3f0acc3fd4434315ebbb8f3dc38a9db4e33b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Autophagy - drug effects</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cartilage, Articular - drug effects</topic><topic>Cartilage, Articular - metabolism</topic><topic>Cartilage, Articular - pathology</topic><topic>Chloroquine - pharmacology</topic><topic>Chondrocytes - drug effects</topic><topic>Chondrocytes - metabolism</topic><topic>Chondrocytes - pathology</topic><topic>Danio rerio</topic><topic>Embryo, Nonmammalian</topic><topic>Gene Expression Regulation</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Lysosomal Membrane Proteins - genetics</topic><topic>Lysosomal Membrane Proteins - metabolism</topic><topic>Lysosomes - drug effects</topic><topic>Lysosomes - metabolism</topic><topic>Membrane Proteins - antagonists & inhibitors</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondrial Proteins - antagonists & inhibitors</topic><topic>Mitochondrial Proteins - genetics</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Molecular Medicine</topic><topic>Morpholinos - genetics</topic><topic>Morpholinos - metabolism</topic><topic>Original Article</topic><topic>Osteoarthritis - genetics</topic><topic>Osteoarthritis - metabolism</topic><topic>Osteoarthritis - pathology</topic><topic>Peroxisomes - drug effects</topic><topic>Peroxisomes - metabolism</topic><topic>Primary Cell Culture</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Signal Transduction</topic><topic>Zebrafish - embryology</topic><topic>Zebrafish - genetics</topic><topic>Zebrafish - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Dongkyun</creatorcontrib><creatorcontrib>Song, Jinsoo</creatorcontrib><creatorcontrib>Kang, Yeonho</creatorcontrib><creatorcontrib>Park, Sujung</creatorcontrib><creatorcontrib>Kim, Yong-Il</creatorcontrib><creatorcontrib>Kwak, Seongae</creatorcontrib><creatorcontrib>Lim, Dongkwon</creatorcontrib><creatorcontrib>Park, Raekil</creatorcontrib><creatorcontrib>Chun, Churl-Hong</creatorcontrib><creatorcontrib>Choe, Seong-Kyu</creatorcontrib><creatorcontrib>Jin, Eun-Jung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>Journal of molecular medicine (Berlin, Germany)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Dongkyun</au><au>Song, Jinsoo</au><au>Kang, Yeonho</au><au>Park, Sujung</au><au>Kim, Yong-Il</au><au>Kwak, Seongae</au><au>Lim, Dongkwon</au><au>Park, Raekil</au><au>Chun, Churl-Hong</au><au>Choe, Seong-Kyu</au><au>Jin, Eun-Jung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function</atitle><jtitle>Journal of molecular medicine (Berlin, Germany)</jtitle><stitle>J Mol Med</stitle><addtitle>J Mol Med (Berl)</addtitle><date>2016-12-01</date><risdate>2016</risdate><volume>94</volume><issue>12</issue><spage>1373</spage><epage>1384</epage><pages>1373-1384</pages><issn>0946-2716</issn><eissn>1432-1440</eissn><abstract>Cumulative evidence suggests the importance of organelle homeostasis in regulating metabolic functions in response to various cellular stresses. Particularly, the dynamism and health of the mitochondria-peroxisome network through fission and fusion are essential for cellular function; dysfunctional dynamism underlies the pathogenesis of several degenerative diseases including Parkinson’s disease. Here, we investigated the role of Fis1 in cartilage homeostasis and its relevance to osteoarthritis (OA). We found that Fis1 is significantly suppressed in human OA chondrocytes compared to that in normal chondrocytes. Fis1 depletion through siRNA induced peroxisomal dysfunction. Moreover, Fis1 suppression altered miRNA profiles, especially those implicated in lysosomal regulation. Lysosomal destruction using LAMP-1-specific targeted nanorods or lysosomal dysfunction through chloroquine treatment resulted in enhanced chondrocyte apoptosis and/or suppression of autophagy. Accordingly, lysosomal activity and autophagy were severely decreased in OA chondrocytes despite abundant LAMP-1-positive organelles. Moreover, Fis1 morpholino-injected zebrafish embryos displayed lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction. Collectively, these data suggest interconnected links among Fis1-modulated miRNA, lysosomes, and autophagy, which contributes to chondrocyte survival/apoptosis. This study represents the first functional study of Fis1 with its pathological relevance to OA. Our data suggest a new target for controlling cartilage-degenerative diseases, such as OA.
Key message
Fis1 suppression in OA chondrocytes induces accumulation and inhibition of lysosomes.
Fis1 suppression alters miRNAs, especially those implicated in lysosomal regulation.
Lysosomal destruction results in chondrocyte apoptosis and suppression of autophagy.
Fis1 depletion in zebrafish causes lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction.
This is the first functional study of Fis1 and its pathological relevance to OA.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>27497958</pmid><doi>10.1007/s00109-016-1445-9</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0946-2716 |
| ispartof | Journal of molecular medicine (Berlin, Germany), 2016-12, Vol.94 (12), p.1373-1384 |
| issn | 0946-2716 1432-1440 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1868331877 |
| source | MEDLINE; SpringerLink |
| subjects | Animals Apoptosis - drug effects Autophagy - drug effects Biomedical and Life Sciences Biomedicine Cartilage, Articular - drug effects Cartilage, Articular - metabolism Cartilage, Articular - pathology Chloroquine - pharmacology Chondrocytes - drug effects Chondrocytes - metabolism Chondrocytes - pathology Danio rerio Embryo, Nonmammalian Gene Expression Regulation Human Genetics Humans Internal Medicine Lysosomal Membrane Proteins - genetics Lysosomal Membrane Proteins - metabolism Lysosomes - drug effects Lysosomes - metabolism Membrane Proteins - antagonists & inhibitors Membrane Proteins - genetics Membrane Proteins - metabolism MicroRNAs - genetics MicroRNAs - metabolism Mitochondria - drug effects Mitochondria - metabolism Mitochondrial Proteins - antagonists & inhibitors Mitochondrial Proteins - genetics Mitochondrial Proteins - metabolism Molecular Medicine Morpholinos - genetics Morpholinos - metabolism Original Article Osteoarthritis - genetics Osteoarthritis - metabolism Osteoarthritis - pathology Peroxisomes - drug effects Peroxisomes - metabolism Primary Cell Culture RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Signal Transduction Zebrafish - embryology Zebrafish - genetics Zebrafish - metabolism |
| title | Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T14%3A50%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fis1%20depletion%20in%20osteoarthritis%20impairs%20chondrocyte%20survival%20and%20peroxisomal%20and%20lysosomal%20function&rft.jtitle=Journal%20of%20molecular%20medicine%20(Berlin,%20Germany)&rft.au=Kim,%20Dongkyun&rft.date=2016-12-01&rft.volume=94&rft.issue=12&rft.spage=1373&rft.epage=1384&rft.pages=1373-1384&rft.issn=0946-2716&rft.eissn=1432-1440&rft_id=info:doi/10.1007/s00109-016-1445-9&rft_dat=%3Cproquest_cross%3E4272022561%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1846649793&rft_id=info:pmid/27497958&rfr_iscdi=true |