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 the aberration of different OXPHOS complexes in human cells. We demonstrate here that the complete disruption of each of the OXPHOS complexes resulted in a decrease in the complex I (cI) level and that the major reason for this is linked to the 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.

Department of Biomedical Sciences University of Padova 35131 Padova Italy

Department of Cell Biology Faculty of Science Charles University 12800 Prague Czech Republic

Department of Genetics and Microbiology Faculty of Science Charles University 12800 Prague Czech Republic

Department of Pediatrics and Inherited Diseases 1st Faculty of Medicine Charles University 12108 Prague Czech Republic

Department of Physiology Faculty of Science Charles University 12800 Prague Czech Republic

Laboratory for Study of Mitochondrial Disorders 1st Faculty of Medicine Charles University and General University Hospital 12808 Prague Czech Republic

Laboratory of Bioenergetics Institute of Physiology Czech Academy of Sciences 14200 Prague Czech Republic

Laboratory of Molecular Therapy Institute of Biotechnology Czech Academy of Sciences 25250 Prague Czech Republic

School of Pharmacy and Medical Science Griffith University Southport Qld 4222 Australia

Veneto Institute of Molecular Medicine 35129 Padova Italy

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