Mitochondrial ATP synthase: architecture, function and pathology

Jonckheere, An I.; Smeitink, Jan A.M.; Rodenburg, Richard J.

doi:10.1007/s10545-011-9382-9

Cited by 470 publications

(380 citation statements)

References 150 publications

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“…Complex V phosphorylates ADP to produce ATP by utilizing the electrochemical gradient produced during CI to CIV electron transfer [90].…”

Section: Oxphos Complex Vmentioning

confidence: 99%

“…Pathogenic mutations to MTATP6 [92] can result in maternally inherited Leigh syndrome (MILS) [93] and neuropathy, ataxia, retinal pigmentosa (NARP) [90,92]. Additionally, mutations to CV assembly factors, TMEM70 [94] and ATPAF2 [95] have been identified and present with cardiomyopathy, hypotonia, intrauterine growth restriction and oligohydramnios [94,95] (Table 1).…”

Section: Oxphos Complex Vmentioning

confidence: 99%

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Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

2016

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SynopsisMitochondria provide the main source of energy to eukaryotic cells, oxidizing fats and sugars to generate ATP . Mitochondrial fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are two metabolic pathways which are central to this process. Defects in these pathways can result in diseases of the brain, skeletal muscle, heart and liver, affecting approximately 1 in 5000 live births. There are no effective therapies for these disorders, with quality of life severely reduced for most patients. The pathology underlying many aspects of these diseases is not well understood; for example, it is not clear why some patients with primary FAO deficiencies exhibit secondary OXPHOS defects. However, recent findings suggest that physical interactions exist between FAO and OXPHOS proteins, and that these interactions are critical for both FAO and OXPHOS function. Here, we review our current understanding of the interactions between FAO and OXPHOS proteins and how defects in these two metabolic pathways contribute to mitochondrial disease pathogenesis.Key words: disease, mitochondria, protein complex assembly, protein interactions, supercomplex. MITOCHONDRIAL METABOLISMMitochondria occupy almost all human cell types and are involved in essential metabolic and cellular processes, including calcium and iron homoeostasis, apoptosis, innate immunity and haeme biosynthesis [1]. However, the primary function of mitochondria is the production of energy in the form of ATP [2][3][4]. ATP is the body's energy currency, playing vital roles in cell differentiation, growth and reproduction, thermogenesis and powering the contraction of muscles for movement [1]. In humans, ATP is produced by two different processes; through the breakdown of glucose or other sugars in Abbreviations: ACAD9, acyl-CoA dehydrogenase 9; BN-PAGE, blue native polyacrylamide gel electrophoresis; CACT, carnitine acylcarnitine translocase; CI, oxidative phosphorylation complex I (NADH: ubiquinone oxidoreductase, EC 1.6.5.3); CII, oxidative phosphorylation complex II (succinate: ubiquinone oxidoreductase, EC 1.3.5.1); CIII, oxidative phosphorylation complex III (ubiquinol: ferricytochrome c oxidoreductase, EC 1.10.2.2); CIV, oxidative phosphorylation complex IV (cytochrome c oxidase, EC 1.9.3.1); COPP , complex one phylogenetic profile; CPT1, carnitine O-palmitoyltransferase 1; CPT2, carnitine O-palmitoyltransferase 2; CV, OXPHOS complex V (FoF 1 -ATP synthetase, EC; 3.6.3.14); ECHS1, enoyl-CoA hydratase, short chain 1, mitochondrial; ECI1, enoyl-CoA delta isomerase, 1; ETF, electron transfer flavoprotein; ETFA, electron transfer flavoprotein alpha subunit; ETFB, electron transfer flavoprotein beta subunit; ETF-QO, electron transfer flavoprotein: ubiquinone oxidoreductase; FAD, flavin adenine dinucleotide; FADH 2 , reduced flavin adenine dinucleotide; FAO, fatty acid β-oxidation; H 2 O, water; HADH, hydroxyacyl-CoA dehydrogenase; KAT, 3-ketoacyl-CoA thiolase, mitochondrial; LCAD, long chain acyl-CoA dehydrogenase; LCEH, long chain enoyl-CoA hydra...

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“…Complex V phosphorylates ADP to produce ATP by utilizing the electrochemical gradient produced during CI to CIV electron transfer [90].…”

Section: Oxphos Complex Vmentioning

confidence: 99%

Section: Oxphos Complex Vmentioning

confidence: 99%

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

2016

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“…[2] At micromolar concentrations 1 inhibited F 0 F 1 -ATPase by binding with subunit F 0 and blocking OSCP (oligomycin sensitivity conferring protein). [3] Previously a series of modifications at the side chain and chemical transformation of the lactone moiety of 1 have been developed. [4][5][6][7][8] However, all derivatives modificated at the lactone moiety were less potent than 1.…”

Section: Corresponding Author E-mail: Shchekotikhin@mailrumentioning

confidence: 99%

Synthesis and Biological Activity of 2,3,16,17,18,19-Hexahydrooligomycin A

Omelchuk¹,

Belov²,

Цветков³

et al. 2016

MHC

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“…Two previous publications suggested that ATP5B might be involved in mitochondrial dynamics. Wang et al demonstrated that small molecule M1 promotes the mitochondrial fusion by increasing ATP5A/B (Wang et al 2012) and Jonckheere et al have reported mitochondrial fragmentation and dysfunction from a mitochondrial complex V (ATP5B included) deficient mutations in patient fibroblasts (Jonckheere et al 2011;Jonckheere et al 2012). Such changes in mitochondrial shape have been shown to directly impact cell differentiation and proliferation (Ahn & Metallo 2015); however, little is known as to how ATP5B regulates the phenotype and metabolic characteristics of mitochondria.…”

Section: Introductionmentioning

confidence: 99%

ATP5B regulates mitochondrial fission and fusion in mammalian cells

Seo

Lee

Chung

et al. 2016

Animal Cells and Systems

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Mitochondria are essential organelles that produce ATP and regulate cell growth, proliferation, and cell death. To maintain homeostasis, fusion and fission of mitochondria must be strictly regulated. Even though oligomerization of ATP synthase could affect the mitochondrial morphology, the exact mechanism is not clear. We confirmed that structure and function of ATP5B, which is a major component of the catalytic center of ATP synthase complexes, are closely connected to the mitochondrial morphology. ATP5B itself can enhance elongation of mitochondria. Moreover, mutations of the threonine residue at β-barrel domain, and the serine residue at nucleotidebinding domain of ATP5B, produce the opposite effect on the fission and fusion of mitochondrial networks. Here, we demonstrate that ATP5B is clearly involved in the mechanism of regulation for mitochondrial fusion and fission in mammalian cells. ARTICLE HISTORY

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Mitochondrial ATP synthase: architecture, function and pathology

Cited by 470 publications

References 150 publications

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

Synthesis and Biological Activity of 2,3,16,17,18,19-Hexahydrooligomycin A

ATP5B regulates mitochondrial fission and fusion in mammalian cells

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