Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems

Overview

Journal Annu Rev Pathol

Publisher Annual Reviews

Specialty Pathology

Date 2017 Nov 4

PMID 29099651

Citations 16

Authors

Adam J Kuszak

Michael Graham Espey

Marni J Falk

Marissa A Holmbeck

Giovanni Manfredi

Gerald S Shadel

Hilary J Vernon

Zarazuela Zolkipli-Cunningham

Affiliations

Soon will be listed here.

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.

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