PT  - JOURNAL ARTICLE
AU  - Damiecki, Melissa
AU  - Naha, Ritam
AU  - Schaumkessel, Yulia
AU  - Westhoff, Philipp
AU  - Atanelov, Nika
AU  - Stefanski, Anja
AU  - Petzsch, Patrick
AU  - Stühler, Kai
AU  - Köhrer, Karl
AU  - Weber, Andreas PM
AU  - Anand, Ruchika
AU  - Reichert, Andreas S
AU  - Kondadi, Arun Kumar
TI  - Mitochondrial apolipoprotein MIC26 is a metabolic rheostat regulating central cellular fuel pathways
AID  - 10.26508/lsa.202403038
DP  - 2024 Dec 01
TA  - Life Science Alliance
PG  - e202403038
VI  - 7
IP  - 12
4099  - https://www.life-science-alliance.org/content/7/12/e202403038.short
4100  - https://www.life-science-alliance.org/content/7/12/e202403038.full
SO  - Life Sci. Alliance2024 Dec 01; 7
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.