Mitochondrial Protein Quality Control Mechanisms

Molecular mechanisms of spatial protein quality control

Evidence is now accumulating that damaged proteins are not randomly distributed but often concentrated in microscopically visible and functionally distinct inclusion bodies. How misfolded proteins are organized into these compartments, however, is still unknown. We have recently begun to investigate stress-inducible protein quality control (PQC) bodies in yeast cells. Surprisingly, we found tha...

Mechanisms of mitochondrial quality control in autosomal recessive Parkinson’s disease

MicroRNAs (miRNAs) are short, 22–25 nucleotide long transcripts that may suppress entire signaling pathways by interacting with the 3’-untranslated region (3’-UTR) of coding mRNA targets, interrupting translation and inducing degradation of these targets. The long 3’-UTRs of brain transcripts compared to other tissues predict important roles for brain miRNAs. Supporting this notion, we found th...

SnapShot: Mitochondrial Quality Control

Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics.

Mitochondrial dysfunction is associated with a broad range of pathologies including diabetes, ethanol toxicity, metabolic syndrome and cardiac failure. It is now becoming clear that maintaining mitochondrial quality through a balance between biogenesis, reserve capacity and mitophagy is critical in determining the response to metabolic or xenobiotic stress. In diseases associated with metabolic...

Mechanisms of mitochondrial protein import.

Mitochondria import most of their proteins from the cytosol. Precursor forms of most matrix proteins as well as some IM and IMS proteins are synthesized on cytoplasmic ribosomes with N-terminal cleavable signal sequences. Many other mitochondrial proteins including IM carrier proteins contain internal targeting sequences. Three multisubunit translocases, one in the OM and two in the IM, partici...