Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection

ABSTRACT: Lysosomal cathepsins regulate an exquisite range of biological functions, and their deregulation is associated with inflammatory, metabolic and degenerative disease in humans. Here, we identified a key cell-intrinsic role for cathepsin B as a negative feedback regulator of lysosomal biogenesis and autophagy. Mice and macrophages lacking cathepsin B activity had increased resistance to the cytosolic bacterial pathogen Francisella novicida. Genetic deletion or pharmacological inhibition of cathepsin B downregulated mTOR activity and prevented cleavage of the lysosomal calcium channel TRPML1. These events drove transcription of lysosomal and autophagy genes via the transcription factor TFEB, which increased lysosomal biogenesis and activation of autophagy-initiation kinase ULK1 for clearance

ORGANISM(S): Mus musculus

SUBMITTER: Geoffrey Neale 

PROVIDER: E-GEOD-79508 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress