ONLINE COVER Shining a Light on Mitochondrial Damage. Elevated type I interferon (IFN) in the epidermis of individuals with the autoimmune disorder cutaneous lupus erythromatosus (CLE) enhances photosensitivity to ultraviolet B (UVB) light, which can trigger localized and systemic inflammation. Klein et al. show that UVB exposure of keratinocytes from the skin of patients with CLE causes the oxidation of their mitochondrial DNA (mtDNA). This mtDNA is released into the cytoplasm in the Z-DNA conformation, where it is stabilized by IFN-induced Z-DNA–binding protein 1 (ZBP1). The Z-DNA–ZBP1 complex strongly activates cGAS-STING signaling, which fuels additional type I IFN production. These results highlight how by-products of UVB-induced mitochondrial damage can drive CLE-associated inflammation. This month’s cover features a keratinocyte mitochondrion damaged by UVB radiation, which then releases reactive oxygen species (red spheres) and Z-DNA complexed with ZBP1 into the cytoplasm.