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

Fingerprint

Mitochondrial Diseases
Oxidative Phosphorylation
Animal Models
Micronutrients
Nutritive Value
Randomized Controlled Trials
Safety
Mutation
Health
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kuszak, A. J., Espey, M. G., Falk, M. J., Holmbeck, M. A., Manfredi, G., Shadel, G. S., ... Zolkipli-Cunningham, Z. (2018). Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems. Annual Review of Pathology: Mechanisms of Disease, 13, 163-191. https://doi.org/10.1146/annurev-pathol-020117-043644

Nutritional Interventions for Mitochondrial OXPHOS Deficiencies : Mechanisms and Model Systems. / Kuszak, Adam J.; Espey, Michael Graham; Falk, Marni J.; Holmbeck, Marissa A.; Manfredi, Giovanni; Shadel, Gerald S.; Vernon, Hilary J; Zolkipli-Cunningham, Zarazuela.

In: Annual Review of Pathology: Mechanisms of Disease, Vol. 13, 24.01.2018, p. 163-191.

Research output: Contribution to journalReview article

Kuszak, Adam J. ; Espey, Michael Graham ; Falk, Marni J. ; Holmbeck, Marissa A. ; Manfredi, Giovanni ; Shadel, Gerald S. ; Vernon, Hilary J ; Zolkipli-Cunningham, Zarazuela. / Nutritional Interventions for Mitochondrial OXPHOS Deficiencies : Mechanisms and Model Systems. In: Annual Review of Pathology: Mechanisms of Disease. 2018 ; Vol. 13. pp. 163-191.
@article{e553dd7aaea64105948c2f1e0757657d,
title = "Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems",
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.",
keywords = "Electron transport chain, Metabolism, Nutritional interventions, Primary mitochondrial OXPHOS disorders",
author = "Kuszak, {Adam J.} and Espey, {Michael Graham} and Falk, {Marni J.} and Holmbeck, {Marissa A.} and Giovanni Manfredi and Shadel, {Gerald S.} and Vernon, {Hilary J} and Zarazuela Zolkipli-Cunningham",
year = "2018",
month = "1",
day = "24",
doi = "10.1146/annurev-pathol-020117-043644",
language = "English (US)",
volume = "13",
pages = "163--191",
journal = "Annual Review of Pathology: Mechanisms of Disease",
issn = "1553-4006",
publisher = "Annual Reviews Inc.",

}

TY - JOUR

T1 - Nutritional Interventions for Mitochondrial OXPHOS Deficiencies

T2 - Mechanisms and Model Systems

AU - Kuszak, Adam J.

AU - Espey, Michael Graham

AU - Falk, Marni J.

AU - Holmbeck, Marissa A.

AU - Manfredi, Giovanni

AU - Shadel, Gerald S.

AU - Vernon, Hilary J

AU - Zolkipli-Cunningham, Zarazuela

PY - 2018/1/24

Y1 - 2018/1/24

N2 - 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.

AB - 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.

KW - Electron transport chain

KW - Metabolism

KW - Nutritional interventions

KW - Primary mitochondrial OXPHOS disorders

UR - http://www.scopus.com/inward/record.url?scp=85041702747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041702747&partnerID=8YFLogxK

U2 - 10.1146/annurev-pathol-020117-043644

DO - 10.1146/annurev-pathol-020117-043644

M3 - Review article

VL - 13

SP - 163

EP - 191

JO - Annual Review of Pathology: Mechanisms of Disease

JF - Annual Review of Pathology: Mechanisms of Disease

SN - 1553-4006

ER -