OPA1 drives macrophage metabolism and functional commitment via p65 signaling

• DOI: 10.1038/s41418-022-01076-y
• Publication Date: 2022-10-28T19:08:25Z
• Authors: Ricardo Sánchez-R...; Caterina Tezze; Andrielly H. R. A...; Roberta Angioni; Francisca C. Venegas; Chiara Cioccarelli; Fabio Munari; Nicole Bertoldi; Marcella Canton; Maria Andrea Desbats; Leonardo Salviati; Rosanna Gissi; Alessandra Castegna; Maria Eugenia Sor...; Marco Sandri; Luca Scorrano; Antonella Viola; Barbara Molon
• Keywords: 0301 basic medicine; 03 medical and health sciences; Macrophages; Mitochondrial Membranes; Article; Mitochondria; Signal Transduction

Abstract Macrophages are essential players for the host response against pathogens, regulation of inflammation and tissue regeneration. The wide range macrophage functions rely on their heterogeneity plasticity that enable a dynamic adaptation responses according to surrounding environmental cues. Recent studies suggest metabolism provides synergistic support activation elicitation desirable immune responses; however, metabolic pathways orchestrating still under scrutiny. Optic atrophy 1 (OPA1) is mitochondria-shaping protein controlling mitochondrial fusion, cristae biogenesis respiration; clear evidence shows lack or dysfunctional activity this triggers accumulation intermediates TCA cycle. In study, we show OPA1 has crucial role in activation. Selective Opa1 deletion myeloid cells impairs M1-macrophage commitment. Mechanistically, leads cycle metabolite defective NF-κB signaling an vivo model muscle regeneration upon injury, knockout macrophages persist within damaged tissue, leading excess collagen deposition impairment Collectively, our data indicate key driver functions.