RT Journal Article
SR Electronic
T1 Mitochondrial apolipoprotein MIC26 is a metabolic rheostat regulating central cellular fuel pathways
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202403038
DO 10.26508/lsa.202403038
VO 7
IS 12
A1 Damiecki, Melissa
A1 Naha, Ritam
A1 Schaumkessel, Yulia
A1 Westhoff, Philipp
A1 Atanelov, Nika
A1 Stefanski, Anja
A1 Petzsch, Patrick
A1 Stühler, Kai
A1 Köhrer, Karl
A1 Weber, Andreas PM
A1 Anand, Ruchika
A1 Reichert, Andreas S
A1 Kondadi, Arun Kumar
YR 2024
UL https://www.life-science-alliance.org/content/7/12/e202403038.abstract
AB Mitochondria play central roles in metabolism and metabolic disorders such as type 2 diabetes. MIC26, a mitochondrial contact site and cristae organising system complex subunit, was linked to diabetes and modulation of lipid metabolism. Yet, the functional role of MIC26 in regulating metabolism under hyperglycemia is not understood. We used a multi-omics approach combined with functional assays using WT and MIC26 KO cells cultured in normoglycemia or hyperglycemia, mimicking altered nutrient availability. We show that MIC26 has an inhibitory role in glycolysis and cholesterol/lipid metabolism under normoglycemic conditions. Under hyperglycemia, this inhibitory role is reversed demonstrating that MIC26 is critical for metabolic adaptations. This is partially mediated by alterations of mitochondrial metabolite transporters. Furthermore, MIC26 deletion led to a major metabolic rewiring of glutamine use and oxidative phosphorylation. We propose that MIC26 acts as a metabolic “rheostat,” that modulates mitochondrial metabolite exchange via regulating mitochondrial cristae, allowing cells to cope with nutrient overload.The mass spectrometry proteomics data from this publication have been deposited to the PRIDE partner repository and assigned the identifier PXD047246. The transcriptomics data from this publication have been deposited to the NCBI’s Gene Expression Omnibus (GEO) database and assigned the GEO series accession number GSE248848.