Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems

Adam J. Kuszak, Michael Graham Espey, Marni J. Falk, Marissa A. Holmbeck, Giovanni Manfredi, Gerald S. Shadel, Hilary J. Vernon, Zarazuela Zolkipli-Cunningham

Research output: Contribution to journalReview article

Abstract

Multisystem metabolic disorders caused by defects in oxidative phosphorylation (OXPHOS) are severe, often lethal, conditions. Inborn errors of OXPHOS function are termed primary mitochondrial disorders (PMDs), and the use of nutritional interventions is routine in their supportive management. However, detailed mechanistic understanding and evidence for efficacy and safety of these interventions are limited. Preclinical cellular and animal model systems are important tools to investigate PMD metabolic mechanisms and therapeutic strategies. This review assesses the mechanistic rationale and experimental evidence for nutritional interventions commonly used in PMDs, including micronutrients, metabolic agents, signaling modifiers, and dietary regulation, while highlighting important knowledge gaps and impediments for randomized controlled trials. Cellular and animal model systems that recapitulate mutations and clinical manifestations of specific PMDs are evaluated for their potential in determining pathological mechanisms, elucidating therapeutic health outcomes, and investigating the value of nutritional interventions for mitochondrial disease conditions.

Original languageEnglish (US)
Pages (from-to)163-191
Number of pages29
JournalAnnual Review of Pathology: Mechanisms of Disease
Volume13
DOIs
StatePublished - Jan 24 2018

Keywords

  • Electron transport chain
  • Metabolism
  • Nutritional interventions
  • Primary mitochondrial OXPHOS disorders

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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