Year: 2026
Type: article
Abstract: to sustain glyceraldehyde-3-phosphate dehydrogenase activity. This regeneration is mediated by three main pathways: lactate dehydrogenase, the glycerol-3-phosphate shuttle, and the malate-aspartate shuttle (MASh). We previously showed that inhibition of the mitochondrial pyruvate carrier increases energy expenditure in brown adipocytes via MASh activation. However, the specific contribution of MASh to BAT energy metabolism remains poorly defined. Here, we show that MASh is functional and directly regulates lipid metabolism in BAT. Enzymatic activities of cytosolic and mitochondrial malate dehydrogenases and glutamic-oxaloacetic transaminases in BAT were comparable to those in the liver. Using a reconstituted system of isolated BAT mitochondria and cytosolic MASh enzymes, we demonstrated that extra-mitochondrial NADH is efficiently reoxidized in a glutamate-dependent manner via MASh. Genetic silencing of the mitochondrial carriers critical to MASh-namely the oxoglutarate carrier (OGC1) and aspartate-glutamate carrier (Aralar1) had no apparent effects on respiratory rates. However, silencing either OGC1 or Aralar1 led to the accumulation of small lipid droplets and impaired norepinephrine-induced lipolysis. Taken together, our data indicate a novel role of MASh in regulating BAT lipid homeostasis with potential implications to body energy expenditure and thermogenesis.
Source: FEBS Journal
DOI: 10.1111/febs.70461
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Funders: European Commission, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, National Institutes of Health, European Regional Development Fund, Agencia Estatal de Investigación, National Institute of Diabetes and Digestive and Kidney Diseases, NIH Clinical Center
Awards: G116629194, G1175115578, G1380260072, G1686041357, G1840770272, G210041235, G2127023913, G2262748287, G2311368543, G233101189, G255675270, G2601397997, ANTS RESEARCH GROUP EVOLUTION TO A RESEARCH EXCELLENCE INSTITUTE, G2881695692, G29316538, G300979063, G3220167584, G3226431920, G34346518, G3480869486, G3585261522, G3681454997, G3742211480, G4042783231, G410571670, G425668148, G451917667, G4596055754, G487239277, G4934285840, G5080475149, G5218949221, G5584990930, G5967599077, G645722556, G6815844370, G739134416, G7434936867, Mitochondrial regulation of energy efficiency, G929308097
OpenAlex ID: W7130467305