Building a Beautiful Beast: Mammalian Respiratory Complex I.

Understanding the mammalian respiratory complex I assembly has been an arduous task due to the lack of appropriate techniques and the complexity of the process. In this issue, a new tour de force based on complexome profiling provides an encyclopedic description of the process (Guerrero-Castillo et al., 2017).

Mechanism of super-assembly of respiratory complexes III and IV.

Respiratory chain complexes can super-assemble into quaternary structures called supercomplexes that optimize cellular metabolism. The interaction between complexes III (CIII) and IV (CIV) is modulated by supercomplex assembly factor 1 (SCAF1, also known as COX7A2L). The discovery of SCAF1 represented strong genetic evidence that supercomplexes exist in vivo.

A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function.

The mitochondrial genome relies heavily on post-transcriptional events for its proper expression, and misregulation of this process can cause mitochondrial genetic diseases in humans. Here, we report that a novel translational variant of Fas-activated serine/threonine kinase (FASTK) co-localizes with mitochondrial RNA granules and is required for the biogenesis of ND6 mRNA, a mitochondrial-encoded subunit of the NADH dehydrogenase complex (complex I). We show that ablating FASTK expression in cultured cells and mice results specifically in loss of ND6 mRNA and reduced complex I activity in vivo.