Bioenergetics, the origins of complexity, and the ascent of man

ArticleinProceedings of the National Academy of Sciences 107 Suppl 2(Suppl 2):8947-53 · May 2010with10 Reads
DOI: 10.1073/pnas.0914635107 · Source: PubMed
Abstract
Complex structures are generated and maintained through energy flux. Structures embody information, and biological information is stored in nucleic acids. The progressive increase in biological complexity over geologic time is thus the consequence of the information-generating power of energy flow plus the information-accumulating capacity of DNA, winnowed by natural selection. Consequently, the most important component of the biological environment is energy flow: the availability of calories and their use for growth, survival, and reproduction. Animals can exploit and adapt to available energy resources at three levels. They can evolve different anatomical forms through nuclear DNA (nDNA) mutations permitting exploitation of alternative energy reservoirs, resulting in new species. They can evolve modified bioenergetic physiologies within a species, primarily through the high mutation rate of mitochondrial DNA (mtDNA)-encoded bioenergetic genes, permitting adjustment to regional energetic environments. They can alter the epigenomic regulation of the thousands of dispersed bioenergetic genes via mitochondrially generated high-energy intermediates permitting individual accommodation to short-term environmental energetic fluctuations. Because medicine pertains to a single species, Homo sapiens, functional human variation often involves sequence changes in bioenergetic genes, most commonly mtDNA mutations, plus changes in the expression of bioenergetic genes mediated by the epigenome. Consequently, common nDNA polymorphisms in anatomical genes may represent only a fraction of the genetic variation associated with the common "complex" diseases, and the ascent of man has been the product of 3.5 billion years of information generation by energy flow, accumulated and preserved in DNA and edited by natural selection.
    • "We argue that this growing attention for mitochondrial biology, and its increasing relevance to modern medicine (McBride, 2015; Pagliarini and Rutter, 2013), is attributable to the convergence of key signaling pathways and biological processes onto the mitochondrion. As life evolved from unicellular organisms over the last 1.2-1.5 billion years, mitochondria played a permissive role in the evolution of multicellular organisms (Lane and Martin, 2010; Wallace, 2010), even though the exact timing of endosymbiosis is under debate (Pittis and Gabaldon, 2016). Most likely as a result of this evolutionary connection to the basic cellular circuitry (), mitochondria are intimately linked to a number of basic cellular and physiological functions (Nunnari and Suomalainen, 2012). "
    [Show abstract] [Hide abstract] ABSTRACT: Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential cellular functions beyond energy production, impacting most areas of cell biology and medicine. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980's, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mitochondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems. Novel “mitopathogenic” mechanisms are thus being uncovered across a number of medical disciplines including genetics, oncology, neurology, immunology, and critical care medicine. Increasing knowledge of the bioenergetic aspects of human disease has provided new opportunities for diagnosis, therapy, prevention, and in connecting various domains of medicine. In this article, we overview specific aspects of mitochondrial biology that have contributed to – and likely will continue to enhance the progress of modern medicine.
    Full-text · Article · Jul 2016
    • "Environmental variation is tied to climate, geology, luminosity, and seasonality, thus supporting that the NP is population-or location-specific. Energy allocation and metabolism as strategies of human adaptation to diverse environments are used to model underlying causal relationships in human phenotypic variation (Wallace, 2010).Thomas et al. (1989)demonstrate the accommodation of the holistic anthropological models to include the nutrition as a component in modeling energy flow, fertility patterns, and related factors examining populations from Africa, Peru and others. Anthropological studies examining effects of energy allocation trade-off with ultimate effects on evolution include Aiello and Wheeler (1995) and subsequent interpretations illustrate a bioenergetics approach to explain early evolutionary changes: increased nutrient density from meats, leading to decreased gut metabolic apparatus, resulting in increased capacity for mobilization and hunting, thus providing additional variety of nutrients (Anton et al., 2002). "
    [Show abstract] [Hide abstract] ABSTRACT: Epigenetic mechanisms have been widely studied for the past several decades, yet despite a surfeit of literature examining animal models and extensive human research associating these mechanisms with pathology, little is known regarding the normal variation among populations or the phenotypic relevance of that variation. Moreover, no one is certain of the evolutionary significance these mechanisms and their underlying machinery. Their structure and function are highly dependent upon dietary intake of indispensable nutrients, yet nutrient profiles vary across populations and generations in an ongoing manner and energy intake can fluctuate dramatically. Here, we examine how the DNA methylation might archive ancestral dietary patterns and discuss the initial findings in a pilot study on population variation in DNA methylation patterns in four maternal/offspring duos from three continents (n = 88). This pilot examined DNA methylation patterns across the core promoter of the metabolic gene leptin (LEP), a leading regulator of energy homeostasis and adipogenesis. Remarkably similar overall mean patterns were present across 7 CpG sites which include the C/EBPα transcription binding site, and two sites proximal to the TATA. Findings suggest a stable and conserved DNA methylation pattern in this region of the (LEP) promoter across populations consuming diets from varying food chains.
    Full-text · Article · Nov 2015 · Biochemistry and Cell Biology
    • "Acetyl-CoA is generated primarily in the mitochondria, but can also be synthesized in the nucleus (Wallace 2010, Sutendra, Kinnaird et al. 2014). In addition, ATP is important for folate metabolism and synthesis of the methyl donor SAM (Wallace 2010). Indeed, it has been shown that altered mitochondrial content results in significant changes in DNA methylation of a number of nuclear genes and may contribute to tumorigenesis (Smiraglia, Kulawiec et al. 2008), suggesting that the mitochondrial function may modulate DNA methylation and histone modifications of the nuclear genome. "
    [Show abstract] [Hide abstract] ABSTRACT: β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of β cell identity, which is characterized by reduced expression of genes that are important for β cell function, ectopic expression of genes that are not supposed to be expressed in β cells, and loss of genetic imprinting. Consequently, this may lead to β cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes.
    Full-text · Article · Aug 2015
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