Mitochondrial Respiration Controls Lysosomal Function during Inflammatory T Cell Responses

摘要: The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how compartment regulated by mitochondrial function largely unknown. We have generated a mouse model with defective in CD4(+) T lymphocytes genetic deletion transcription factor A (Tfam). Mitochondrial respiration deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation, disrupts trafficking pathways autophagy, thus linking primary dysfunction to lysosomal storage disorder. impaired Tfam-deficient cells subverts cell differentiation toward proinflammatory subsets exacerbates vivo inflammatory response. Restoration NAD(+) levels improves corrects defects cells. Our results uncover mechanism which mitochondria regulate preserve effector functions, identify strategies intervention mitochondrial-related diseases.