Mitochondria are one of the major ancient endomembrane systems in eukaryotic cells. Owing to their ability to produce ATP through respiration, they became a driving force in evolution. As an essential step in the process of eukaryotic evolution, the size of the mitochondrial chromosome was drastically reduced, and the behaviour of mitochondria within eukaryotic cells radically changed.
Recent advances have revealed how the organelle’s behaviour has evolved to allow the accurate transmission of its genome and to become responsive to the needs of the cell and its own dysfunction.
Mitochondria arose around two billion years ago from the engulfment of an α-proteobacterium by a precursor of the modern eukaryotic cell. Although mitochondria have maintained the double membrane character of their ancestors and the core of ATP production, their overall form and composition have been drastically altered, and they have acquired myriad additional functions within the cell.
As part of the process of acquiring new functions during evolution, most of the genomic material of the α-proteobacterium progenitor was rapidly lost or transferred to the nuclear genome. What remains in human cells is a small, approximately 16 kilobase, circular genome, which is present in cells in a vast excess of copies relative to nuclear chromosomes. The human mitochondrial genome contains genetic coding information for 13 proteins, which are core constituents of the mitochondrial respiratory complexes I–IV that are embedded in the inner membrane.
Functioning together with the Krebs’ cycle in the matrix, the respiratory chain creates an electrochemical gradient through the coupled transfer of electrons to oxygen and the transport of protons from the matrix across the inner membrane into the intermembrane space. The electrochemical gradient powers the terminal complex V of the chain, ATP synthase, which is an ancient rotary turbine machine that catalyses the synthesis of most cellular ATP.
The electrochemical potential is harnessed for additional crucial mitochondrial functions, such as buffering the signalling ion Ca2+ through uptake by a uniporter in the inner membrane. A reduction in the electrochemical potential of mitochondria in cells has evolved as a read-out for mitochondrial functional status, which, as discussed later, creates signals to activate pathways that repair and/or eliminate defective mitochondria. (Nature 505, 335–343 (16 January 2014) doi:10.1038/nature12985)