ACTA1 and systemic sclerosis: Mitochondrial function was evaluated using Seahorse assays alongside mitochondrial protein synthesis assessments.<h4>Results</h4>Linezolid inhibited TGFβ-induced fibroblast activation in cultured human fibroblasts, SScSE, sclGvHD mice, and SSc-PCSS, as demonstrated by reversal of profibrotic gene expression programs, downregulation of TGFβ, WNT, and JAK-STAT signaling, and reductions in αSMA expression or stress fiber formation, which led to reduced collagen deposition and ameliorated skin or lung fibrosis in vivo.