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A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine
Author(s) -
Wallace Douglas Cecil
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1474-c
Subject(s) - mitochondrial dna , mitochondrion , biology , disease , genetics , somatic cell , cancer , epigenetics , gene , human mitochondrial genetics , bioinformatics , medicine , pathology
Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by‐product, it is hypothesized that mitochondrial dysfunction plays a central role in a wide range of age‐related disorders including metabolic deficiencies like diabetes, neurodegenerative diseases like Alzheimer and Parkinson disease, aging and various forms of cancer. The mitochondrial energy system is assembled from the products of both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) genes. Since the mtDNA is present in thousands of copies per cell and encodes essential genes for energy production, it is further proposed that the delayed‐onset and progressive course of the age‐related diseases results from the accumulation of somatic mutations in the mtDNAs of post‐mitotic tissues. The tissue‐specific manifestations of these diseases are envisioned to result from the varying energetic roles and needs of the different tissues which are the result of differential expression of key nuclear regulatory factors. The variation in individual and regional predisposition to degenerative diseases and cancer is hypothesized to result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms that permitted ancestral humans to adapt to the various environments that they encountered as they migrated around the globe. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbearers to energetically adapt to their ancestral homes are influencing our health today.