No role for nuclear transcription regulators in mammalian mitochondria?
Diana Rubalcava-Gracia, Rodolfo García-Villegas, Nils‐Göran Larsson
Abstract
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-1α, and hormone receptors, are imported into mammalian mitochondria and directly interact with the mtDNA transcription machinery. However, the supporting experimental evidence for this concept is open to alternate interpretations, 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 discussion and experimental guidelines to stringently assess roles of intramitochondrial factors implicated in direct regulation of mammalian mtDNA transcription.