The Mitochondrial Proteome and Human Disease

The Mitochondrial Proteome and Human Disease


Defining the mitochondrial proteome is not a straightforward task: not all mitochondrial proteins possess a targeting sequence to direct their import into the organelle; abundance spans 6 orders of magnitude; and almost half of mitochondrial proteins are distributed in a tissue-specific manner. Surprisingly, it appears that complexes I, II, III and V are found in high abundance across many tissues but complex IV has a fair number of subunits which are expressed in a tissue-dependent manner, as well as many of the mitochondrial ribosome subunits. The most successful way of determining the mitochondrial proteome to date, has been with mass spectrometry by purifying mitochondrial extracts. It is believed that 1100-1400 distinct gene loci encode mitochondrial proteins, but these may also have splice isoforms. The authors also provide a list of useful online databases for mitochondrial proteins. 

The authors discuss how the definition of mitochondrial disease has expanded from disorders of oxidative ATP production, to include diseases such as soft tissue tumours and diabetes mellitus. They suggest that a promising avenue to elucidate mitochondrial disorders is to combine disease genes, clinical features and biological pathways.