Mitochondrial protein heterogeneity


Our cells are addicted to energy. Whether it is protein synthesis, DNA replication, autophagy or signal transduction, almost every biological process is driven by the consumption of energy. To meet this demand, our cells contain hundreds, or even thousands of mitochondria that fuel our cells with ATP. Since every compartment in our cells requires its own energy supply, mitochondria are usually distributed throughout the cell body, not unlike a power grid, to ensure that all demands are met. By rewiring this power grid (or in other words, by changing the location of mitochondria), a cell can respond to changes in its environment or its own intrinsic needs; thus, the multiplicity of mitochondria, combined with their mobility, helps to solve the energy crisis of our cells. It is important to realize though, that this solution contains an inherent drawback. Mitochondria contain approximately a thousand unique proteins, and the vast majority of these proteins are encoded in the nucleus and imported into the mitochondria after translation. However, each mitochondrion must contain each of these proteins in the correct stoichiometry ratio for optimal function. How does a cell achieve this task? Can a cell scan the entire proteome of each mitochondrion and then supply that mitochondrion with the exact protein it misses? These considerations highlight a problem that is central to the biology of all multifarious organelles: the more organelles you create, the harder it is to control the quality of each individual unit. Our laboratory is working on the visualization of this problem using clever combinations of fluorescent markers, so that we can dissect the mechanisms that maintain the proteome of individual organelles.

Related Publications

Chen HC*, Vermulst M*, Wang YE, Prolla TA, McCaffery MJ and Chan DC. (2010) Mitochondrial fusion is required for mtDNA stability and tolerance of mtDNA mutations. Cell 141, 280‐289. PMID: 20403324. PMCID: PMC2858759   * equal contributors

Haroon S, Vermulst M. Linking mitochondrial dynamics to mitochondrial protein quality control Curr Opin Genet Dev. 2016 Jun;38:68-74. doi: 10.1016/j.gde.2016.04.004. Epub 2016 May 25. Review.