The ketogenic diet as a therapeutic intervention strategy in mitochondrial disease. (September 2021)

• Record Type: Journal Article
• Authors: Qu, Changbo; Keijer, Jaap; Adjobo-Hermans, Merel J.W.; van de Wal, Melissa; Schirris, Tom; van Karnebeek, Clara; Pan, Yihang; Koopman, Werner J.H.
• Is Part Of: International journal of biochemistry & cell biology. Volume 138(2021)
• Publication Date: 2021-09
• Subjects: ACA acetoacetate -- AcCoA acetyl coenzyme A -- AMPK AMP-activated protein kinase -- β-HAD β-hydroxyacyl-CoA dehydrogenase -- BHB β-hydroxybutyrate -- C10 decanoic acid -- CI-CV complex I to complex V -- CS citrate synthase -- CAT catalase -- ETC electron transport chain -- ETF electron-transferring flavoprotein -- FA fatty acid -- FADH2 flavin adenine dinucleotide -- FAO fatty acid oxidation -- FATP fatty acid transfer protein -- FGF21 Fibroblast growth factor 21 -- GCL glutamate cysteine ligase -- GLUTs glucose transporters -- GPX glutathione peroxidase -- GR glutathione reductase -- GSH reduced glutathione -- GS glutathione synthase -- GSSG oxidized glutathione -- HDACs histone deacetylases -- KD ketogenic diet -- LCAD long-chain acyl-CoA dehydrogenase -- LS Leigh syndrome -- LHON Leber's hereditary optic neuropathy -- LKB1 liver kinase B1 -- mAD modified Atkins Diet -- MCAD medium-chain acyl-CoA dehydrogenase -- MCT-KD medium-chain triglyceride ketogenic diet -- Mfn2 mitofusin 2 -- MD mitochondrial disease -- MELAS Mitochondrial encephalopathy lactic acidosis, and stroke-like episodes -- MIM mitochondrial inner membrane -- mPT mitochondrial permeability transition -- mPTP mitochondrial permeability transition pore -- mTORC1 mammalian target of rapamycin complex 1 -- mtDNA mitochondrial DNA -- NAD+ oxidized nicotinamide adenine dinucleotide -- NADH reduced nicotinamide adenine dinucleotide -- NAMPT nicotinamide phosphoribosyltransferase -- nDNA nuclear DNA -- NNT nicotinamide nucleotide transhydrogenase -- NRF2 nuclear factor erythroid-derived 2-related factor 2 -- OXPHOS oxidative phosphorylation -- PARP polyADP ribose polymerase -- PEO Progressive external ophthalmoplegia -- PI3K Phosphatidylinositol 3-kinase -- PPP pentose phosphate pathway -- PRDX3 peroxiredoxin 3 -- ROS reactive oxygen species -- SCFAs short chain fatty acids -- SOD superoxide dismutase -- TCA tricarboxylic acid -- TRXR2 thioredoxin reductase 2 -- TRXS2 oxidized thioredoxin -- TRX(SH)2 reduced thioredoxin -- UCPs uncoupling proteins -- VLCAD very-long-chain acyl-CoA dehydrogenase; Mitochondria -- Mitochondrial disease -- Ketone bodies -- Bioenergetics; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2021.106050
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Classical mitochondrial disease (MD) represents a group of complex metabolic syndromes primarily linked to dysfunction of the mitochondrial ATP-generating oxidative phosphorylation (OXPHOS) system. To date, effective therapies for these diseases are lacking. Here we discuss the ketogenic diet (KD), being a high-fat, moderate protein, and low carbohydrate diet, as a potential intervention strategy. We concisely review the impact of the KD on bioenergetics, ROS/redox metabolism, mitochondrial dynamics and mitophagy. Next, the consequences of the KD in (models of) MD, as well as KD adverse effects, are described. It is concluded that the current experimental evidence suggests that the KD can positively impact on mitochondrial bioenergetics, mitochondrial ROS/redox metabolism and mitochondrial dynamics. However, more information is required on the bioenergetic consequences and mechanistic mode-of-action aspects of the KD at the cellular level and in MD patients.