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Pathogenic mitochondrial dysfunction and metabolic abnormalities

Journal

BIOCHEMICAL PHARMACOLOGY
Volume 193, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2021.114809

Keywords

Mitochondrial diseases; Disorders; Dysfunction; Metabolic abnormalities; Diseases; Homeostasis; Pathogenesis; Reprogramming; Biochemical pathways; Physiological networks; Pathogenesis and pathogenic drivers; Therapeutics

Funding

  1. MitoCure Foundation

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This article traces the connections between biochemical pathways, pathogenesis, and metabolic diseases, emphasizing the crucial role of mitochondria in metabolic disorders and the genetic, metabolic, and mitochondrial factors in various diseases such as diabetes and heart failure.
Herein we trace links between biochemical pathways, pathogenesis, and metabolic diseases to set the stage for new therapeutic advances. Cellular and acellular microorganisms including bacteria and viruses are primary pathogenic drivers that cause disease. Missing from this statement are subcellular compartments, importantly mitochondria, which can be pathogenic by themselves, also serving as key metabolic disease intermediaries. The breakdown of food molecules provides chemical energy to power cellular processes, with mitochondria as powerhouses and ATP as the principal energy carrying molecule. Most animal cell ATP is produced by mitochondrial synthase; its central role in metabolism has been known for >80 years. Metabolic disorders involving many organ systems are prevalent in all age groups. Progressive pathogenic mitochondrial dysfunction is a hallmark of genetic mitochondrial diseases, the most common phenotypic expression of inherited metabolic disorders. Confluent genetic, metabolic, and mitochondrial axes surface in diabetes, heart failure, neurodegenerative disease, and even in the ongoing coronavirus pandemic.

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