Loss Of The Ubiquitin-Conjugating Enzyme Rad6b Disturbs Mitochondrial Function And Cellular Homeostasis In Mouse Skin

Various factors can induce cell degeneration by altering the phenotype and metabolism of cells. Mitochondria play an essential role in cellular homeostasis and function, rendering aging processes highly associated with mitochondrial function and status. Herein, we describe an aging-prone phenotype of murine skin cells caused by depletion of Rad6B (Ube2b), an E2 ubiquitin-conjugating enzyme. In this study, using Masson's trichrome, we showed that loss of Rad6B causes physiological structure changes in mouse skin with age. In addition, a combination of western blotting experiments, transmission electron microscopy and employment of immunofluorescence staining revealed that depletion of Rad6B was characterized by an abnormal mitochondrial metabolic profile, including decreased mitochondrial biosynthesis and mitochondrial complex activities, increased ROS production and suppressed mitophagy resulting in metabolic disorders. Taken together, these results highlight an important relationship between Rad6B and skin senescence, suggesting that Rad6B plays an indispensable role in maintaining a healthy mitochondrial network and intracellular homeostasis.