Year: 2016
Type: editorial
Abstract: Cysteine cathepsins are responsible for driving proteolytic degradation within the lysosome and in the extralysosomal milieu. They also have an integral role in autophagy, antigen presentation, cellular stress signaling, metabolism and lysosome-dependent cell death. Here, we discuss our findings on the role of CTSB (cathepsin B), a member of the cysteine cathepsin family, in regulating the bioavailability of lysosomes and autophagosomes and consider how this regulatory response influences host susceptibility to infectious agents. Our study demonstrates that under homeostatic conditions CTSB cleaves the calcium channel MCOLN1/TRPML1 in the lysosomes, maintaining suppression of the transcription factor TFEB and reducing expression of lysosomal and autophagy-related proteins. This response controls the number of lysosomes and autophagosomes in the cell. However, the activity of CTSB is exploited by the cytosolic bacterium Francisella novicida, leading to enhanced survival of the pathogen and increased susceptibility of the host to infection.
Source: Autophagy
Authors: Si Ming Man, Thirumala-Devi Kanneganti
Institution: St. Jude Children's Research Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: American Lebanese Syrian Associated Charities, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
OpenAlex ID: W2545511601