Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction

Abstract Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular...

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Autores principales:	Susan Giorgi-Coll, Ana I. Amaral, Peter J. A. Hutchinson, Mark R. Kotter, Keri L. H. Carpenter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e35d43f0d3549c7bfdec73a8e038567
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spelling	oai:doaj.org-article:1e35d43f0d3549c7bfdec73a8e0385672021-12-02T15:18:52ZSuccinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction10.1038/s41598-017-01149-w2045-2322https://doaj.org/article/1e35d43f0d3549c7bfdec73a8e0385672017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01149-whttps://doaj.org/toc/2045-2322Abstract Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular energy state under metabolically stressed conditions in a robust, reductionist in vitro model of mitochondrial dysfunction in which primary mixed glial cultures (astrocytes, microglia and oligodendrocytes) were exposed to the mitochondrial complex I inhibitor rotenone. Cellular response was determined by measuring intracellular ATP, extracellular metabolites (glucose, lactate, pyruvate), and oxygen consumption rate (OCR). Rotenone produced no significant changes in glial ATP levels. However, it induced metabolic deficits as evidenced by lactate/pyruvate ratio (LPR) elevation (a clinically-established biomarker for poor outcome in TBI) and decrease in OCR. Succinate addition partially ameliorated these metabolic deficits. We conclude that succinate can improve glial oxidative metabolism, consistent our previous findings in TBI patients’ brains. The mixed glial cellular model may be useful in developing therapeutic strategies for conditions involving mitochondrial dysfunction, such as TBI.Susan Giorgi-CollAna I. AmaralPeter J. A. HutchinsonMark R. KotterKeri L. H. CarpenterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Susan Giorgi-Coll Ana I. Amaral Peter J. A. Hutchinson Mark R. Kotter Keri L. H. Carpenter Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction
description	Abstract Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular energy state under metabolically stressed conditions in a robust, reductionist in vitro model of mitochondrial dysfunction in which primary mixed glial cultures (astrocytes, microglia and oligodendrocytes) were exposed to the mitochondrial complex I inhibitor rotenone. Cellular response was determined by measuring intracellular ATP, extracellular metabolites (glucose, lactate, pyruvate), and oxygen consumption rate (OCR). Rotenone produced no significant changes in glial ATP levels. However, it induced metabolic deficits as evidenced by lactate/pyruvate ratio (LPR) elevation (a clinically-established biomarker for poor outcome in TBI) and decrease in OCR. Succinate addition partially ameliorated these metabolic deficits. We conclude that succinate can improve glial oxidative metabolism, consistent our previous findings in TBI patients’ brains. The mixed glial cellular model may be useful in developing therapeutic strategies for conditions involving mitochondrial dysfunction, such as TBI.
format	article
author	Susan Giorgi-Coll Ana I. Amaral Peter J. A. Hutchinson Mark R. Kotter Keri L. H. Carpenter
author_facet	Susan Giorgi-Coll Ana I. Amaral Peter J. A. Hutchinson Mark R. Kotter Keri L. H. Carpenter
author_sort	Susan Giorgi-Coll
title	Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction
title_short	Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction
title_full	Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction
title_fullStr	Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction
title_full_unstemmed	Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction
title_sort	succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1e35d43f0d3549c7bfdec73a8e038567
work_keys_str_mv	AT susangiorgicoll succinatesupplementationimprovesmetabolicperformanceofmixedglialcellcultureswithmitochondrialdysfunction AT anaiamaral succinatesupplementationimprovesmetabolicperformanceofmixedglialcellcultureswithmitochondrialdysfunction AT peterjahutchinson succinatesupplementationimprovesmetabolicperformanceofmixedglialcellcultureswithmitochondrialdysfunction AT markrkotter succinatesupplementationimprovesmetabolicperformanceofmixedglialcellcultureswithmitochondrialdysfunction AT kerilhcarpenter succinatesupplementationimprovesmetabolicperformanceofmixedglialcellcultureswithmitochondrialdysfunction
_version_	1718387434399465472

Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction

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