No role for nuclear transcription regulators in mammalian mitochondria?

Although the mammalian mtDNA transcription machinery is simple and resembles bacteriophage systems, there are many reports that nuclear transcription regulators, as exemplified by MEF2D, MOF, PGC-1a, and hormone receptors, are imported into mammalian mitochondria and directly interact with the mtDNA tran-scription machinery. However, the supporting experimental evidence for this concept is open to alternate in-terpretations, and a main issue is the difficulty in distinguishing indirect regulation of mtDNA transcription, caused by altered nuclear gene expression, from direct intramitochondrial effects. We provide a critical dis-cussion and experimental guidelines to stringently assess roles of intramitochondrial factors implicated in direct regulation of mammalian mtDNA transcription.

Automated summary

Despite the simplicity of mammalian mtDNA transcription machinery, there is evidence that nuclear transcription regulators can directly interact with it. However, the experimental evidence for this concept is open to alternate interpretations. Differentiating between indirect regulation caused by altered nuclear gene expression and direct intramitochondrial effects is a main challenge. This study provides critical discussions and experimental guidelines to assess the roles of intramitochondrial factors in direct regulation of mammalian mtDNA transcription.