Screening of protein kinase inhibitors and knockdown experiments identified four kinases that affect mitochondrial ATP synthesis activity
•We searched for a protein kinase that affects mitochondrial ATP synthesis in HeLa cells.•We screened 80 protein kinase inhibitors.•Four inhibitors affected the level of mitochondrial ATP synthesis.•Knockdown of the inhibitors’ target kinases results in reduced ATP synthesis.•The ATP synthase popula...
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Veröffentlicht in: | FEBS letters 2013-11, Vol.587 (23), p.3843-3847 |
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Zusammenfassung: | •We searched for a protein kinase that affects mitochondrial ATP synthesis in HeLa cells.•We screened 80 protein kinase inhibitors.•Four inhibitors affected the level of mitochondrial ATP synthesis.•Knockdown of the inhibitors’ target kinases results in reduced ATP synthesis.•The ATP synthase population was decreased by MLCK (myosin light chain kinase)-knockdown.
Mitochondrial ATP synthase, a major ATP supplier in respiring cells, should be regulated in amount and in activity to respond to the varying demands of cells for ATP. We screened 80 protein kinase inhibitors and found that HeLa cells treated with four inhibitors exhibited reduced mitochondrial ATP synthesis activity. Consistently, knockdown of their target kinases (PKA, PKCδ, CaMKII and smMLCK) resulted in a decrease in mitochondrial ATP synthesis activity. Among them, mitochondria of smMLCK-knockdown cells contained only a small amount of ATP synthase, while the α- and β-subunits of ATP synthase were produced normally, suggesting that smMLCK affects assembly (or decay) of ATP synthase. |
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ISSN: | 0014-5793 1873-3468 |
DOI: | 10.1016/j.febslet.2013.10.012 |