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 are cellular organelles critical for ATP biosynthesis and have been dubbed the " powerhouses of the cell " (Lane and Martin, 2010; Wallace, 2007). Mitochondria are largely thought to be evolutionarily derived from endosymbiotic α-proteobacteria species (Gabaldon and Huynen, 2004; Gray, 2012; Knoll, 2012; Kurland and Andersson, 2000; Nunnari and Suomalainen, 2012). "
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    ABSTRACT: Epigenetic modifications of the nuclear genome have been well studied and it is established that these modifications play a key role in nuclear gene expression. However, the status of mitochondrial epigenetic modifications has not been delved in detail. The recent technological advancements in the genome analyzing tools and techniques, have helped in investigating mitochondrial epigenetic modifications with greater resolution and studies have indicated a regulatory role of the mitochondrial epigenome. Association of mitochondrial DNA methylation with various disease conditions, drug treatment, aging, exposure to environmental pollutants etc. has lent credence to this belief. Herein, we have reviewed studies on mitochondrial epigenetic modifications with a focus to comprehend its regulatory role in gene expression and disease association.
    Mitochondrion 10/2015; 25. DOI:10.1016/j.mito.2015.09.003 · 3.25 Impact Factor
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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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    ABSTRACT: Cancer is a heterogeneous set of diseases characterized by different molecular and cellular features. Over the past decades, researchers have attempted to grasp the complexity of cancer by mapping the genetic aberrations associated with it. In these efforts, the contribution of mitochondria to the pathogenesis of cancer has tended to be neglected. However, more recently, a growing body of evidence suggests that mitochondria play a key role in cancer. In fact, dysfunctional mitochondria not only contribute to the metabolic reprogramming of cancer cells but they also modulate a plethora of cellular processes involved in tumorigenesis. In this review, we describe the link between mutations to mitochondrial enzymes and tumor formation. We also discuss the hypothesis that mutations to mitochondrial and nuclear DNA could cooperate to promote the survival of cancer cells in an evolving metabolic landscape.
    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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