Prohibitin-1 plays a regulatory role in Leydig cell steroidogenesis.

Mitochondria are essential for steroidogenesis. In steroidogenic cells, the initiation of steroidogenesis from cholesterol occurs on the matrix side of the inner mitochondrial membrane by the enzyme P450scc. This requires cholesterol import from the cytoplasm through the outer mitochondrial membrane, facilitated by the StAR protein.

The intracellular cholesterol pool in steroidogenic cells plays a role in basal steroidogenesis.

The framework of steroidogenesis across steroidogenic cells is constructed around cholesterol - the precursor substrate molecule for all steroid hormones - including its cellular uptake, storage in intracellular lipid droplets, mobilization upon steroidogenic stimulation, and finally, its transport to the mitochondria, where steroidogenesis begins. Thus, cholesterol and the mitochondria are highly interconnected in steroidogenic cells. Moreover, accruing evidence suggests that autophagy and mitochondrial dynamics are important cellular events in the regulation of trophic hormone-induced cholesterol homeostasis and steroidogenesis.

The Expanding Role of Mitochondria, Autophagy and Lipophagy in Steroidogenesis.

The fundamental framework of steroidogenesis is similar across steroidogenic cells, especially in initial mitochondrial steps. For instance, the START domain containing protein-mediated cholesterol transport to the mitochondria, and its conversion to pregnenolone by the enzyme P450scc, is conserved across steroidogenic cells. The enzyme P450scc localizes to the inner mitochondrial membrane, which makes the mitochondria essential for steroidogenesis.

Inter-proteomic posttranslational modifications of the SARS-CoV-2 and the host proteins ‒ A new frontier.

Posttranslational modification of proteins, which include both the enzymatic alterations of protein side chains and main-chain peptide bond connectivity, is a fundamental regulatory process that is crucial for almost every aspects of cell biology, including the virus-host cell interaction and the SARS-CoV-2 infection. The posttranslational modification of proteins has primarily been studied in cells and tissues in an intra-proteomic context (where both substrates and enzymes are part of the same species). However, the inter-proteomic posttranslational modifications of most of the SARS-CoV-2 proteins by the host enzymes and are largely unexplored in virus pathogenesis and in the host immune response.

Sex Differences in Immunometabolism: An Unexplored Area.

The last three decades have seen a growing interest in research in the field of immunometabolism, likely because of promising discoveries made in this field. This includes demonstration of the crucial roles of cellular metabolism in the regulation of functional plasticity of various immune cells, their cross talk with major metabolic tissues (and consequently in the regulation of metabolic homeostasis) at the systemic level, and their potential in improving the efficacy of current immunotherapy or developing new therapeutics for a variety of metabolic and immune diseases (Lee YS, Wollam J, Olefsky JM, Cell 172:22-40, 2018). Surprisingly, sex differences, which are integral to metabolic and immune health and disease, have received a short shrift from researchers in this field.

Prohibitin: a prime candidate for a pleiotropic effector that mediates sex differences in obesity, insulin resistance, and metabolic dysregulation.

Adipocytes and macrophages, the two major constituents of adipose tissue, exhibit sex differences and work in synergy in adipose tissue physiology and pathophysiology, including obesity-linked insulin resistance and metabolic dysregulation. Sex steroid hormones play a major role in sex differences in adipose tissue biology. However, our knowledge of the molecules that mediate these effects in adipose tissue remains limited.