Som 2023 Am J Physiol Cell Physiol: Difference between revisions
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|title=Som R, Fink BD, Yu L, Sivitz WI (2023) Oxaloacetate regulates complex II respiration in brown fat: dependence on UCP1 expression. Am J Physiol Cell Physiol 324:C1236-48. doi: 10.1152/ajpcell.00565.2022 | |title=Som R, Fink BD, Yu L, Sivitz WI (2023) Oxaloacetate regulates complex II respiration in brown fat: dependence on UCP1 expression. Am J Physiol Cell Physiol 324:C1236-48. doi: 10.1152/ajpcell.00565.2022 | ||
|info=[https://pubmed.ncbi.nlm.nih.gov/37125774/ PMID: 37125774 | |info=[https://pubmed.ncbi.nlm.nih.gov/37125774/ PMID: 37125774] | ||
|authors=Som R, Fink BD, Yu L, Sivitz WI | |authors=Som R, Fink BD, Yu L, Sivitz WI | ||
|year=2023 | |year=2023 |
Latest revision as of 22:25, 28 October 2023
Som R, Fink BD, Yu L, Sivitz WI (2023) Oxaloacetate regulates complex II respiration in brown fat: dependence on UCP1 expression. Am J Physiol Cell Physiol 324:C1236-48. doi: 10.1152/ajpcell.00565.2022 |
Som R, Fink BD, Yu L, Sivitz WI (2023) Am J Physiol Cell Physiol
Abstract: We previously found that skeletal muscle mitochondria incubated at low membrane potential (ฮฮจ) or interscapular brown adipose tissue (IBAT) mitochondria, wherein ฮฮจ is intrinsically low, accumulate oxaloacetate (OAA) in amounts sufficient to inhibit complex II respiration. We proposed a mechanism wherein low ฮฮจ reduces reverse electron transport (RET) to complex I causing a low NADH/NAD+ ratio favoring malate conversion to OAA. To further assess the mechanism and its physiologic relevance, we carried out studies of mice with inherently different levels of IBAT mitochondrial inner membrane potential. Isolated complex II (succinate)-energized IBAT mitochondria from obesity-resistant 129SVE mice compared with obesity-prone C57BL/6J displayed greater UCP1 expression, similar O2 flux despite lower ฮฮจ, similar OAA concentrations, and similar NADH/NAD+. When GDP was added to inhibit UCP1, 129SVE IBAT mitochondria, despite their lower ฮฮจ, exhibited much lower respiration, twofold greater OAA concentrations, much lower RET (as marked by ROS), and much lower NADH and NADH/NAD+ ratios compared with the C57BL/6J IBAT mitochondria. UCP1 knock-out abolished OAA accumulation by succinate-energized mitochondria associated with markedly greater ฮฮจ, ROS, and NADH, but equal or greater O2 flux compared with WT mitochondria. GDP addition, compared with no GDP, increased ฮฮจ and complex II respiration in wild-type (WT) mice associated with much less OAA. Respiration on complex I substrates followed the more classical dynamics of greater respiration at lower ฮฮจ. These findings support the abovementioned mechanism for OAA- and ฮฮจ-dependent complex II respiration and support its physiological relevance.NEW & NOTEWORTHY We examined mitochondrial respiration initiated at mitochondrial complex II in mice with varying degrees of brown adipose tissue UCP1 expression. We show that, by affecting inner membrane potential, UCP1 expression determines reverse electron transport from complex II to complex I and, consequently, the NADH/NAD+ ratio. Accordingly, this regulates the level of oxaloacetate accumulation and the extent of oxaloacetate inhibition of complex II.
โข Bioblast editor: Gnaiger E โข O2k-Network Lab: US IA Iowa City Sivitz WI
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Obesity
Stress:Oxidative stress;RONS
Organism: Mouse
Tissue;cell: Fat
Preparation: Isolated mitochondria
Enzyme: Complex II;succinate dehydrogenase
Regulation: mt-Membrane potential, Redox state
Pathway: S HRR: Oxygraph-2k, O2k-Fluorometer, TPP
AmR