GDF15 Regulates Mitochondrial Quality Control in Human Skin Fibroblasts

Growth Differentiation Factor 15 (GDF15) is shown to be essential for maintaining mitochondrial quality control in human foreskin fibroblasts. Deficiency of GDF15 leads to a hyperfused, highly branched mitochondrial network, reduced DRP1 abundance, and increased inhibitory phosphorylation of DRP1, causing a severe fission deficit. The altered mitochondria are accompanied by disrupted hypoxia signaling, with diminished nuclear translocation of HIF‑1α and failure to induce BNIP3. GDF15‑deficient cells also exhibit impaired extracellular matrix coordination, inability to form spheroids, and reduced wound‑healing support for neighboring fibroblasts and keratinocytes. These results reposition GDF15 as a regulator of intracellular mitochondrial dynamics and extracellular tissue coordination in skin aging.