Why Do We Still Have a Maternally Inherited Mitochondrial DNA? Insights from Evolutionary Medicine

Center for Molecular and Mitochondrial Medicine and Genetics, Department of Biological Chemistry, University of California, Irvine, California 92697-3940, USA.
Annual Review of Biochemistry (Impact Factor: 30.28). 02/2007; 76(1):781-821. DOI: 10.1146/annurev.biochem.76.081205.150955
Source: PubMed


The human cell is a symbiosis of two life forms, the nucleus-cytosol and the mitochondrion. The nucleus-cytosol emphasizes structure and its genes are Mendelian, whereas the mitochondrion specializes in energy and its mitochondrial DNA (mtDNA) genes are maternal. Mitochondria oxidize calories via oxidative phosphorylation (OXPHOS) to generate a mitochondrial inner membrane proton gradient (DeltaP). DeltaP then acts as a source of potential energy to produce ATP, generate heat, regulate reactive oxygen species (ROS), and control apoptosis, etc. Interspecific comparisons of mtDNAs have revealed that the mtDNA retains a core set of electron and proton carrier genes for the proton-translocating OXPHOS complexes I, III, IV, and V. Human mtDNA analysis has revealed these genes frequently contain region-specific adaptive polymorphisms. Therefore, the mtDNA with its energy controlling genes may have been retained to permit rapid adaptation to new environments.

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    • "Mitochondria contain a circular chromosome of 16,596 base pairs, coding for 37 genes translated into 13 subunits of the respiratory chain and ATPase complexes, 22 tRNAs and 12S and 16S ribosomal RNAs. Mammalian cells contain thousands of copies of mitochondrial DNA (mtDNA) [64]. In contrast to nDNA, mtDNA mutations coexist with normal mtDNA in a heterogeneous mixture known as heteroplasmy. "
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    07/2014; 2(1):10. DOI:10.1186/2049-3002-2-10
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    • "We briefly discuss the possible roles of variations in mitochondrial metabolic phenotypes in predisposition to neurodegenerative diseases among individuals belonging to different mtDNA haplogroups. several fundamental reviews by one of the " Fathers " of Mitochondrial Medicine D.C. Wallace, investigations of mitochondrial physiology and biochemistry failed to give clear answers on the mechanisms that underlie connections between mtDNA haplogroups and pathology [1] [3] [4]. "
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    ABSTRACT: Mitochondria play an important role in adaptation of organisms to changing environmental conditions and type of food. Human mitochondrial DNA (mtDNA) has discrete branches with a group of related mtDNA sequences called a haplogroup. D. C. Wallace stressed that people with different haplogroups have different predisposition to various pathological conditions [1]. Mitochondrial dysfunctions are important in pathogenesis of many major pathologies, particularly neurodegenerative diseases. In this review we analyze the current hypotheses regarding energy metabolism of the brain’s two major cell types - neurons and astroglia. Recently, it was clearly shown that up to 20% of the total brain’s energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrates for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, are transported into neurons and also serve as substrates for mitochondria. Thus neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have important function to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. As a result, it becomes clear that under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We also provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We briefly discuss the possible roles of variations in mitochondrial metabolic phenotypes in predisposition to neurodegenerative diseases among individuals belonging to different mtDNA haplogroups.
    BioMed Research International 05/2014; In press(The Road to Mitochondrial Dysfunctions). DOI:10.1155/2014/472459 · 2.71 Impact Factor
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    • "The emergence and evolution of eukaryotes involved the chimeric union of two genomes now recognized as the nuclear and mitochondrial genomes (Dyall et al. 2004; Lane 2005). Even though these genomes likely began with approximately equal numbers of genes, the great majority of mitochondrial genes (mt genes) migrated to the nuclear genome, leaving only 34 mt genes in vertebrate animals (Lane 2005; Wallace 2007). Mitochondrial processes, however, are extremely complex and multifarious and involve the products of more then 1500 genes (Lopez et al. 2000). "
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