Traditional and novel tools to probe the mitochondrial metabolism in health and disease

Advanced Review

Yanfei Zhang, José L. Avalos

Published Online: Jan 09 2017

DOI: 10.1002/wsbm.1373

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Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α‐ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl‐CoA, iron‐sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer. Therefore, there is great interest in understanding mitochondrial metabolism and the complex relationship it has with other cellular processes. A large number of studies on mitochondrial metabolism have been conducted in the last 50 years, taking a broad range of approaches. In this review, we summarize and discuss the most commonly used tools that have been used to study different aspects of the metabolism of mitochondria: ranging from dyes that monitor changes in the mitochondrial membrane potential and pharmacological tools to study respiration or ATP synthesis, to more modern tools such as genetically encoded biosensors and trans‐omic approaches enabled by recent advances in mass spectrometry, computation, and other technologies. These tools have allowed the large number of studies that have shaped our current understanding of mitochondrial metabolism. WIREs Syst Biol Med 2017, 9:e1373. doi: 10.1002/wsbm.1373 This article is categorized under: Analytical and Computational Methods > Analytical Methods Biological Mechanisms > Metabolism Physiology > Mammalian Physiology in Health and Disease

Tools to probe mitochondrial metabolism. MPCs, mitochondrial pyruvate carrier complex; TCA, citric acid cycle; ROS, reactive oxygen species; BCAAs, branched chain amino acids; FeS, iron‐sulfur clusters; FA, fatty acid; MFA, metabolic flux analysis; OXPHOS, oxidative phosphorylation; ATP, adenosine triphosphate; Q, quinone; C, cytochrome c; NAD, nicotinamide adenine dinucleotide.

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General design of single fluorescent protein‐based biosensor (a, b, c), FRET‐based biosensor (d), and BRET‐based biosensor (e).

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