Failure of OXPHOS components to import is caused by protein accumulation and aggregation in the cytosol or by disruption and blockage of translocase of outer membrane (TOM) transporter which triggers ubiquitination (Ub), leading to proteasomal degradation in the cytosol. Cytosolic degradation may also occur to retro-translocated OXPHOS subunits. Defects in the import and processing of proteins by the intermembrane space MIA40 pathway triggers the retro-translocation of substrates back to the cytosol, rendering the protein prone to ubiquitination and proteasomal degradation.