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Patricia Renard et al.
More precisely, the major co-activator of mitochondrial biogenesis, PGC-1α, and the SIRT1 deacetylase have been shown to be associated with nucleoids in which they interact with TFAM, in association with TFAM consensus binding site, suggesting that these two coactivators might exert a comparable function of transcriptional regulators in both mitochondria and in the nucleus [274]. Clearly, these results add a supplementary layer of control on mitochondria biogenesis to the powerful PGC-1α master coordinator. Although the control on the coordinated expression of both genomes has been mostly described at the transcriptional level, one cannot exclude posttranscriptional coordinated control of the proteins characterized by a dual localization to mitochondria and nuclei. In this case, the coordinated expression between the two compartments, in terms of relative abundance for instance, is not a matter of transcription anymore, but relies on posttranscriptional processes like differential translation initiation. This is the case for the RNase H1 [83] and for the human DNA topoisomerase IIIα (TOP3α) [82]. Each of these transcripts undergoes a differential translation initiation at 2 in-frame AUG start codons of the same mRNA. Regarding the RNaseH1, the preferential use of the first or the second AUG is determined by the presence of a short ORF upstream, and influences the translation level [83]. As we have seen, mitochondrial biogenesis is a very complex process that requires mtDNA abundance control, coordinated protein expression and lipid synthesis to allow mitochondrial population expansion. While an increasingly detailed structural and mechanistic view has been proposed to explain biogenesis, sorting/segregation, and targeting of mitochondrial proteins to the various compartments, mechanisms regulating the supply of phospholipids are, comparatively, less understood and will be the topic of the next section.
2.1.4. Mitochondrial lipid synthesis Mitochondrial phospholipid composition is known to be pretty stable among different cell types, suggesting that major modifications are not allowed. This is probably to put into perspective with the crucial role of mitochondrial phospholipids in mitochondrial structure/morphology and dynamics (regulating fusion-fission events), mitochondrial protein import, integration of signals for cell/survival or apoptosis control and even mtDNA stability and segregation (for a review [275]). The phospholipid compositions of mitochondrial membranes in yeast and mammalian cells are comparable (but slightly different in relative proportions between lipid moieties) and contain roughly 40% phosphatidylcholine