The BBSome Regulates Mitochondria Dynamics and Function

The essential role of mitochondria in physiology and many pathologies has garnered enormous interest in understanding the mechanisms controlling the function of this organelle. The BBSome, a protein complex composed of eight Bardet-Biedl syndrome (BBS) proteins including BBS1, has emerged as an important regulator of various cellular processes. The similarity in the phenotypes evoked by disruption of the BBSome and mitochondria function led us to hypothesize that the BBSome plays an important role in the regulation of mitochondria dynamics and function. To test this, we used a multidisciplinary approach that include CRISPR/Cas9 technology-mediated generation of stable Bbs1 gene knockout cell lines (N39-BBS1KO and IMCD3-BBS1KO) and analysis of the phenotype of global and conditional BBSome deficient mice. Disruption of the BBSome caused mitochondria hyperfusion in cell lines, fibroblasts derived from BBS patients as well as in hypothalamic neurons and brown adipocytes of mice. The morphological changes in mitochondria translate into functional abnormalities as indicated by the altered mitochondrial distribution, reduced oxygen consumption rate and calcium handling responded to PDGFbb stimulation (340/380 ratio, cytosolic Ca2+ 44.0±,5.4 in N39 cells vs 19.5±3.0 in N39-BBS1KO cells, and mitochondria Ca2+, 75.7±4.4 in N39 cells vs11.8±2.1 in N39-BBS1KO cells, P NIH RO1 and VA for K.R This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.