Biology subjects

Yoo, H. S.

Publications and source records attributed to Yoo, H. S..

2 recordsLinked to original sources

bioRxiv2021

Retinoic acid exerts sexually dimorphic effects over muscle energy metabolism and function

The retinol dehydrogenase Rdh10 catalyzes the rate-limiting reaction that converts retinol into retinoic acid (RA), an autacoid that regulates energy balance and suppresses adiposity. Relative to WT, Rdh10+/- males experienced reduced fatty-acid oxidation, glucose intolerance and insulin resistance. Running endurance decreased 40%. Rdh10+/- females increased reliance on fatty acid oxidation and did not experience glucose intolerance nor insulin resistance. Running endurance improved 2.2-fold. Estrogen increased, revealed by a 40% increase in uterine weight. Because skeletal muscle energy use restricts adiposity and insulin resistance, we assessed the mixed fiber type gastrocnemius muscle (GM) to determine the effects of endogenous RA on muscle metabolism in vivo. RA in Rdh10+/- male GM decreased 38% relative to WT. TAG content increased 1.7-fold. Glut1 mRNA and glucose decreased >30%. Rdh10+/- male GM had impaired electron transport chain activity, and a 60% reduction in fasting ATP. The share of oxidative fibers increased, as did expression of the myogenic transcription factors Myog and Myf5. Centralized nuclei increased 5-fold in fibers--indicating muscle malady or repair. In Rdh10+/- female GM, RA decreased only 17%, due to a 1.8-fold increase in the estrogen-induced retinol dehydrogenase, Dhrs9. Rdh10+/- female GM did not amass TAG, increase oxidative fibers, decrease Glut1 mRNA or glucose, nor increase centralized nuclei. Expression of Myog and Myf5 decreased. Electron transport chain activity increased, elevating fasting ATP >3-fold. Thus, small decreases in skeletal muscle RA affect whole body energy use, insulin resistance and adiposity, in part through estrogen-related sexual dimorphic effects on mitochondria function.

biochemistry↗

bioRxiv2021

Role of Gasdermins in the Biogenesis of Apoptotic Cell-Derived Exosomes

The gasdermins, GSDMA, GSDMB, GSDMC, GSDMD, DFNA5, and DFNB59, are a family of pore-forming proteins that has recently been suggested to play a central role in the pyroptosis and the release of inflammatory cytokines. Here, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell-derived exosomes. In apoptotic cells, GADMA, GSDMC, GSDMD, and DFNA5 increased the release of ApoExos, and both their full-length and cleaved forms were localized in the exosomal membrane. GSDMB and DFNB59, on the other hand, negatively affected the release of ApoExos. The caspase-mediated cleavage of gasdermins, especially DFNA5, is suggested to enable cytosolic Ca2+ to flow through endosomal pores and thus increase the biogenesis of ApoExos. In addition, the DFNA5-meidiated biogenesis of ApoExos depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins: annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of ApoExos begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that Dfna5-bearing tumors released ApoExos to induce inflammatory responses in the in vivo 4T1 orthotropic model of breast cancer. The data presented in this study indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.

cell biology↗