| First Author | Som R | Year | 2023 |
| Journal | Am J Physiol Cell Physiol | PubMed ID | 37125774 |
| Mgi Jnum | J:335532 | Mgi Id | MGI:7471281 |
| Doi | 10.1152/ajpcell.00565.2022 | Citation | Som R, et al. (2023) Oxaloacetate regulates complex II respiration in brown fat: dependence on UCP1 expression. Am J Physiol Cell Physiol |
| abstractText | We previously found that skeletal muscle mitochondria incubated at low membrane potential (DeltaPsi) or interscapular brown adipose tissue (IBAT) mitochondria, wherein DeltaPsi is intrinsically low, accumulate oxaloacetate (OAA) in amounts sufficient to inhibit complex II respiration. We proposed a mechanism wherein low DeltaPsi 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 to obesity prone C57BL/6J displayed greater UCP1 expression, similar O(2) flux despite lower DeltaPsi, similar OAA concentrations, and similar NADH/NAD(+). When GDP was added to inhibit UCP1, 129SVE IBAT mitochondria, despite their lower DeltaPsi, exhibited much lower respiration, 2-fold greater OAA concentrations, much lower RET (as marked by ROS), and much lower NADH and NADH/NAD(+) ratios compared to the C57BL/6J IBAT mitochondria. UCP1 knock-out abolished OAA accumulation by succinate-energized mitochondria associated with markedly greater DeltaPsi, ROS, and NADH, but equal or greater O(2) flux compared to WT mitochondria. GDP addition, compared to no GDP, increased DeltaPsi and complex II respiration in wildtype mice associated with much less OAA. Respiration on complex I substrates followed the more classical dynamics of greater respiration at lower DeltaPsi. These findings support the above-mentioned mechanism for OAA- and DeltaPsi-dependent complex II respiration and support its physiological relevance. |
