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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Metab 2015 ; 22 (3): 485-98 Nephropedia Template TP
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Mitochondrial respiration controls lysosomal function during inflammatory T cell responses #MMPMID26299452
Baixauli F; Acín-Pérez R; Villarroya-Beltrí C; Mazzeo C; Nuñez-Andrade N; Gabandé-Rodriguez E; Dolores Ledesma M; Blázquez A; Martin MA; Falcón-Pérez JM; Redondo JM; Enríquez JA; Mittelbrunn M
Cell Metab 2015[Sep]; 22 (3): 485-98 PMID26299452show ga
The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration-deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward pro-inflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify novel strategies for intervention in mitochondrial-related diseases.