The organization and inheritance of the mitochondrial genome

Key Points Mitochondrial DNA (mtDNA) is generally packaged into nucleoids, the heritable units of mtDNA, by the Abf2/TFAM (transcription factor A, mitochondrial)-family of HMG (high mobility group)-box proteins, which are conserved from yeast to humans. However, recent studies have also revealed several metabolic enzymes that are associated with mtDNA in both yeast and vertebrates. The metabolic proteins that are found in yeast mitochondrial nucleoids can substitute for Abf2 in mtDNA packaging and protection when their expression is increased in response to metabolic cues. These findings indicate that the structural organization of mitochondrial nucleoids is subject to remodelling by these metabolically regulated bifunctional proteins. Mitochondrial nucleoid (mt-nucleoid) division can be directly observed by microscopy. The yeast Hsp60 (heat shock protein 60) chaperonin is a bifunctional protein that is involved in this process. Proteins that are involved in mtDNA recombination affect mt-nucleoid number and mtDNA transmissibility. Genes that are involved in mtDNA concatemerization could accelerate the establishment of homoplasmy in dividing cells. Extensive mitochondrial fission leads to the production of mitochondria that are devoid of mt-nucleoids, and transmission of those mitochondria to progeny cells can eventually lead to the loss of mtDNA. Yeast mitochondria are equipped with a membrane-spanning device that physically links mt-nucleoids to the actin cytoskeleton, which provides a mechanism for coupling mitochondrial movement and mtDNA segregation during cell division. mtDNA mutations have causative roles in neuromuscular diseases and cellular ageing. Studies of the organization and inheritance of mt-nucleoids could help us to understand how the mitochondrial genetic system is affected under these conditions. Mitochondrial DNA (mtDNA) encodes essential components of the cellular energy-producing apparatus, and lesions in mtDNA and mitochondrial dysfunction contribute to numerous human diseases. Understanding mtDNA organization and inheritance is therefore an important goal. Recent studies have revealed that mitochondria use diverse metabolic enzymes to organize and protect mtDNA, drive the segregation of the organellar genome, and couple the inheritance of mtDNA with cellular metabolism. In addition, components of a membrane-associated mtDNA segregation apparatus that might link mtDNA transmission to mitochondrial movements are beginning to be identi