The Italian Proteomics Association has begun a research project, the Mitochondrial Proteome Initiative (Mt-HPP), to characterize human mitochondrial DNA-encoded proteins using mass spectrometry. It will integrate with the chromosome-centric (c-HPP) and Biology and Disease Proteome projects (B/D-HPP) currently underway.
The researchers1 intend to define proteomic LC-MS/MS methods to identify and quantify mtDNA-encoded proteins (mtProteins). Their results will create a protein interaction map with special focus on mitochondrial metabolism, and also include characterisation of nuclear-derived proteins active within the organelle.
Mitochondria are essential cell organelles. Described as the power house of the cell, they are responsible for cell metabolic and energy needs as well as other processes such as regulation of apoptosis and buffering intracellular calcium. Mitochondria create energy through oxidative phosphorylation and play a role in the tricarboxlic acid cycle. They are also involved in amino acid, fatty acid, and steroid metabolism as well as control of Reactive Oxygen Species (ROS).
Mitochondria contain their own maternally-inherited genetic material (mtDNA) which encode 37 distinct genes. Many researchers now refer to mitochondria as the 25th human chromosome. To date, approximately 200 human mtDNA mutations have been demonstrated and some of these are associated with conditions such as Parkinson’s disease while others are implicated in the cellular aging process.
Although most of the proteins found inside mitochondria are derived from the cell nucleus, mtProteins encoded by the 37 mitochondrial genes are thought to affect health and development of disease.
Recently, researchers have shown that age-related ROS mitochondrial dysfunction could be an early-stage change in neuro-degenerative disorders such as Parkinson’s and Alzheimer’s diseases. There is also speculation that mitochondria are involved in the pathogenesis and clinical presentation of chronic pain syndromes such as Chronic Fatigue Syndrome and fibromyalgia. Research has found that mitochondria are altered in cancer where tumor cells metabolize substrates differently compared with untransformed cells. This may be at the level of mt-DNA mutations or via nuclear DNA genes that affect mitochondrial function.
Mitochondria may also contribute to diseases such as type 2 diabetes where nutritional intervention and dietary changes can help regulate progression. As well as reacting to nutritional modulation, mitochondria are also sensitive to other external influences; lactobacilli affect cardiomyocytes through mitochondria and HIV infection induces mtDNA change in peripheral blood lymphocytes.
Though mitochondrial output is small compared with nuclear-derived protein translation, the Italian team considers the characterization of its proteome valid. They propose that thoroughly documenting the mitochondrial proteome could uncover potential therapeutic strategies aimed at the cell organelle level. Many of these would be appropriate for early stage disease interventions.
1. Urbani, A., et al. (2013) “The mitochondrial Italian Human Proteome Project initiative (mt-HPP),” Mol. BioSyst., 9, (pp 1984-1992)
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