Ubiquitin-dependent and -independent mitochondrial protein quality controls: implications in ageing and neurodegenerative diseases

The ubiquitin-independent protein quality control of matrix proteins of the mitochondrion is well characterized and until recently the mitochondrion was considered a 'ubiquitination-free' organelle. However, a number of studies now indicate multiple roles of the ubiquitin-proteasome pathway in the regulation and maintenance of mitochondrial integrity. Of particular interest to this review is the finding of a mitochondrial ubiquitin-dependent protein quality control and that this pathway may share similarity to the endoplasmic reticulum-associated degradation (ERAD) pathway that acts to eliminate misfolded proteins from the lumen of the endoplasmic reticulum. The potential cross-talk between the ubiquitin-dependent and -independent protein quality controls and their implications in ageing and neurodegenerative diseases, notably in Parkinson's disease, are discussed.