Tissue-specific responses to TFAM and mtDNA copy number manipulation in prematurely ageing mice.

Somatic mitochondrial DNA (mtDNA) mutations are implicated as important drivers of ageing and age-related diseases. Their pathological effect can be counteracted by increasing the absolute amount of wild-type mtDNA via moderately upregulating TFAM, a protein important for mtDNA packaging and expression. However, strong TFAM overexpression can also have detrimental effects as it results in mtDNA hypercompaction and subsequent impairment of mtDNA gene expression.

Silencing mitochondrial gene expression in living cells.

Mitochondria fulfill central functions in metabolism and energy supply. They express their own genome, which encodes key subunits of the oxidative phosphorylation system. However, the central mechanisms underlying mitochondrial gene expression remain enigmatic, and a lack of suitable technologies to target mitochondrial protein synthesis in cells has limited experimental access.

Identification of TMEM126A as OXA1L-interacting protein reveals cotranslational quality control in mitochondria.

Cellular proteostasis requires transport of polypeptides across membranes. Although defective transport processes trigger cytosolic rescue and quality control mechanisms that clear translocases and membranes from unproductive cargo, proteins that are synthesized within mitochondria are not accessible to these mechanisms. Mitochondrial-encoded proteins are inserted cotranslationally into the inner membrane by the conserved insertase OXA1L.