|Title||Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Kuszak AJ, Espey MGraham, Falk MJ, Holmbeck MA, Manfredi G, Shadel GS, Vernon HJ, Zolkipli-Cunningham Z|
|Journal||Annu Rev Pathol|
|Date Published||2017 Nov 03|
Multisystem metabolic disorders caused by defects in oxidative phosphorylation (OXPHOS) are severe and 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 patterns, 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. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 13 is January 24, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
|Alternate Journal||Annu Rev Pathol|