Biology of mitochondria

Mitochondrial Organization

Mitochondria are double-membrane organelles that are distributed throughout the cytoplasm oif eukaryotic cells as discrete organelles or as a network of interconnected membranes, depending on the tissue, cell stage or environmental condition. The central focus of mitochondria is the electron transport chain and ATP synthase that makes up the system of enzyme complexes that perform oxidative phosphorylation (OXPHOS).

Electron tranport chain and ATP synthesis

The electron tranport chain (ETC) and ATP synthase are multi-subunits enzyme complexes embedded in the inner mitochondrial membrane of mitocjondria. There are four complexes of the ETC (complexes I, II, III, IV) and the fifth complex is ATP synthase.  Electrons enter the chain from compountds derived from nutrients and the electron flow permits the pumping of protons from the matirx into the inter-membrane space, generating a protin gradient.  This energy potential passes through ATP synthae to catalyze the synthesis of ATP from ADP and inorganic phosphate, with the electorns eventually being captured by oxygen molecules. Thus, food and oxygen are your friends.

mtDNA evolution

MtDNA evolves faster than nuclear DNA when the entire mtDNA molecule is considered, but the majority of this pattern is due to faster rates of synonymous site divergence.  When the protein coding regions are considered, mitochondrial proteins actually evovle slower than most nuclear proteins. This pattern implies that mtDNA has a high underlying mutation rate, but purifying selction on mitochondrial protein function eliminates most of these new mutations reducing the substitution rate. Some investigators desperately want mtDNA to illustrate positive Darwininan selection; while this may be true for some of the complex I proteins (ND subunits in the figure), purfying selection is the general rule. The figure shows synonymous (dS), nonsynonymous (dN) and the dN/dS ratio (dark line) across the Drosophila mtDNA protein coding sequence. Figure 7 from Montooth et al. 2009.

Selection on mtDNA and mitonuclear genotypes

Mitochondrial DNA was the first widely used DNA-based marker used in the filed of population and evolutionary genetics.  It was assumed that mtDNA is a neutral marker that provides a window into the population and phylogenetic histories of organisms.  This assmption has been challenged, and increasing evidence shows that mtDNA variation is not neutral. Analyses of mtDNA sequnces show that variation is often (but not always) inconsistent with neutral models of molecular evolution. Functional studies have shown that mtDNA variants alter the fitness of organimss and this fitness effect varies across nuclear genetic backgrounds. Hence, the essense of this question returns to mitonuclear interactions.