Mitochondrial translation is the primary determinant of secondary mitochondrial complex I deficiencies

Individual complexes of the mitochondrial oxidative phosphorylation system (OXPHOS) are not linked solely by their function, they also share dependencies at the maintenance/assembly level, where one complex depends on the presence of a different individual complex. Despite the relevance of this ‘interdependence’ behavior for mitochondrial diseases, its true nature remains elusive. To understand the mechanism that can explain this phenomenon, we examined the consequences of aberration of different OXPHOS complexes in human cells. We demonstrate here that complete disruption of each of OXPHOS complexes resulted in a decrease of complex I (cI) level and that the major reason for this is linked to downregulation of mitochondrial ribosomal proteins. We conclude that the secondary cI defect is due to mitochondrial protein synthesis attenuation, while the responsible signaling pathways could differ based on the origin of the OXPHOS defect.