Mitochondrial gene products

Fig. 12.5. Biogenesis and assembly of cytochrome 6-c, complex in the inner mitochondrial membrane. Cytochrome fc-Cj complex contains at least five different subunits COREI (corl), COREII (corll), nonheme iron protein (Fe-S), cytochrome c, (cyt Cj), and cytochrome b (cyt b). Cytochrome f> is a mitochondrial gene product and is probably assembled into the inner membrane (IM) via vectorial translation by mitochondrial ribosomes. The other subunits are synthesized on cytoplasmic ribosomes as larger precursors. The precursors, perhaps in association with a cytoplasmic factor , are attached to receptors on the mitochondrial outer membrane (OM). The complex laterally diffuses to the junctions of the outer and inner membranes, and with the help of a hypothetical translocator the precursors are imported across the membrane. Pre-Corl, pre-Corll, and the pre-nonheme iron protein cross the two membranes, whereas cytochrome c, becomes anchored to the outer face of the inner membrane, facing the intermembrane space (IMS). Cytochrome b is assembled inside the inner membrane, and the nonheme iron protein and Corl and Corll are assembled into the matrix side of the inner membrane. The N-terminal extensions are removed by a soluble matrix protease. The N-terminal extension of cytochrome c, is removed in two steps the first is catalyzed by the matrix protease and the second probably by a protease located on the outer face of the inner membrane.

Calcium chromate has been shown to induce cytoplasmic petite mutations in mitochondria of Saccharomyces cerevisiae K Calcium chromate also dramatically depressed the content of the mitochondrial gene products cytochrome aa3 and cytochrome b, in whole yeast cells. Chromate ( 8 nM) was readily taken up by rat thymocytes and after 30 min 9% of the Cr was found in the mitochondria although 62% was found in the nuclei . Isolated rat thymus mitochondria and nuclei readily took up CrOj . After one hour incubation of Erlich ascites tumor cells with CrOj (380 /nuclear fraction and 12% was in the mitochondrial-microsomal fraction. Levels of chromium in rat liver mitochondria reached a plateau six hours after i.v. injection of chromate (0.02 mg/kg) and remained at that level through 5 days. Liver nuclear chromium levels in the same animals, although similar to mitochondrial levels at 6 h, reached a maximum at 12 h and steadily decreased after that time. Therefore the nuclear chromium levels were lower than the mitochondrial chromium levels at later times (24-120 h) after injection. The subcellular distribution of chromium in the liver of rats injected i.v. with chromate (0.56 mg/kg) was also found to be time dependent in another study. The distribution of chromium in rat liver mitochondria increased from 5% at 15 min to 21% at 72 h and also increased in the nuclear fraction from 22% at 15 min to 52% at 72 h. Incubation of isolated rat liver mitochondria with chromate (0.3-16.6 electron transport chain of the mitochondrial iner membrane. 

The complex catalyzes electron transfer from reduced UQ to cytochrome c, coupled to the translocation of protons by a mechanism known as the Q cycle [55-57]. This involves the diversion of half of the electrons available from ubiqui-nol oxidation and deprotonation at a site on the outside of the inner mitochondrial membrane (Qo site) to reduce and protonate UQ at a site on the inside of the membrane (Qi site). The pathway for electron transfer across the membrane is provided by the two haem centers (bt and bn) of the mitochondrial gene product cytochrome b. The remainder of the electrons from ubiquinol oxidation pass along the chain to reduce first the Rieske iron sulfur protein (ISP), then cytochrome Cl and then cytochrome c (Fig. 13.1.3). 

Figure 1. Control of mitochondrial biogenesis by the nuclear genome. Most mitochondrial proteins, including cytochrome c, are nuclear gene products which are subsequently imported into mitochondria. Similarly, most enzymes involved in synthesis of mitochondrial phosphoplipids are encoded in the nuclear genome. Being located in the endoplasmatic reticulum, they synthesize phosphatidylcholine (PtdCho), phosphatidylserine (PtdSer), phosphatidylglycerol (PG) and phosphatidylinositol (Ptdins). The phospholipids are transferred to the outer membrane. The imported lipids then move into the inner membrane at contact sites. Mitochondria then diversify phospholipids. They decarboxylate phosphatidylserine to phosphatidylethanolamine (PtdEtN), but the main reaction is the conversion of imported phosphatidylglycerol to cardiolipin (CL). Cardiolipins localize mainly in the outer leaflet of the inner membrane.

Thus, even granted the endosymbiotic origin of mitochondria, the persistence of mitochondrial genes and genomes requires explanation if most ancestral, bacterial genes have been successfully relocated to the cell nucleus, then why not all What is it about mitochondrial genes, or their gene products, that has prevented their successful removal to the nucleus ... 

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