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.
Germain
Doris
D
Mount Sinai School of Medicine, Division of Hematology/Oncology Box 1079, One Gustave L. Levy Place, New York, NY 11029, USA. doris.germain@mssm.edu
D049069:ATP-Dependent Proteases / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
D024101:Mitochondrial Proteins; D025801:Ubiquitin; D049069:ATP-Dependent Proteases; D046988:Proteasome Endopeptidase Complex