title: Identification of a previously undetected metabolic defect in the Complex II Caenorhabditis elegans mev-1 mutant strain using respiratory control analysis.
abstract: Hypometabolism may play an important role in the pathogenesis of ageing and ageing-related diseases. The nematode Caenorhabditis elegans offers the opportunity to study "living mitochondria" in a small (~1 mm) animal replete with a highly stereotypical, yet complex, anatomy and physiology. Basal oxygen consumption rate is often employed as a proxy for energy metabolism in this context. This parameter is traditionally measured using single-chamber Clark electrodes without the addition of metabolic modulators. Recently, multi-well oxygen electrodes, facilitating addition of metabolic modulators and hence study of respiratory control during different mitochondrial respiration states, have been developed. However, only limited official protocols exist for C. elegans, and key limitations of these techniques are therefore unclear. Following modification and testing of some of the existing protocols, we used these methods to explore mitochondrial bioenergetics in live nematodes of an electron transfer chain Complex II mutant strain, mev-1, and identified a previously undetected metabolic defect. We find that mev-1 mutants cannot respond adequately to increased energy demands, suggesting that oxidative phosphorylation is more severely impaired in these animals than has previously been appreciated.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore, National University of Singapore, MD 7, 8 Medical Drive, Singapore, 117596, Singapore.|Internal Medicine Residency Programme, SingHealth Group, Singapore, Singapore.
authors.forename: Sheng
authors.initials: S
authors.lastname: Fong
authors.affiliation: Ageing Research Laboratory, Science Division, Yale-NUS College, Singapore, Singapore.
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Ng
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Li Theng
authors.initials: LT
authors.lastname: Ng
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Ageing Research Laboratory, Science Division, Yale-NUS College, Singapore, Singapore.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore, National University of Singapore, MD 7, 8 Medical Drive, Singapore, 117596, Singapore.
authors.forename: Barry
authors.initials: B
authors.lastname: Halliwell
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore, National University of Singapore, MD 7, 8 Medical Drive, Singapore, 117596, Singapore. jan_gruber@nuhs.edu.sg.|Ageing Research Laboratory, Science Division, Yale-NUS College, Singapore, Singapore. jan_gruber@nuhs.edu.sg.
authors.forename: Jan
authors.initials: J
authors.lastname: Gruber
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D045303:Cytochromes b; D042963:Electron Transport Complex II / Q000235:genetics / Q000378:metabolism*; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010101:Oxygen Consumption; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; C472666:MEV-1 protein, C elegans; D045303:Cytochromes b; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase
keywords: Caenorhabditis elegans; Metabolism; Mitochondria; Oxygen consumption; mev-1