Successful Treatment of Lichen Planus With Oral Upadacitinib.

Lichen planus is an auto-inflammatory skin disorder marked by intensely pruritic, violaceous papules that commonly affect the extremities of middle-aged adults.1 There are several treatment options available, but alternative therapies to target disease refractory to standard interventions remain necessary. Though they have not been FDA-approved for lichen planus, Janus kinase (JAK) inhibitors have demonstrated significant potential as a therapeutic intervention across an array of dermatoses. Herein, we present a case of refractory, biopsy-proven lichen planus successfully treated with the oral JAK1 inhibitor, upadacitinib. J Drugs Dermatol. 2023;22(10):1058-1060     doi:10.36849/JDD.7272.

MDM2 Integrates Cellular Respiration and Apoptotic Signaling through NDUFS1 and the Mitochondrial Network.

Signaling diversity and subsequent complexity in higher eukaryotes is partially explained by one gene encoding a polypeptide with multiple biochemical functions in different cellular contexts. For example, mouse double minute 2 (MDM2) is functionally characterized as both an oncogene and a tumor suppressor, yet this dual classification confounds the cell biology and clinical literatures. Identified via complementary biochemical, organellar, and cellular approaches, we report that MDM2 negatively regulates NADH:ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1), leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis. MDM2 directly binds and sequesters NDUFS1, preventing its mitochondrial localization and ultimately causing complex I and supercomplex destabilization and inefficiency of oxidative phosphorylation. The MDM2 amino-terminal region is sufficient to bind NDUFS1, alter supercomplex assembly, and induce apoptosis. Finally, this pathway is independent of p53, and several mitochondrial phenotypes are observed in Drosophila and murine models expressing transgenic Mdm2.