Cathepsin L Regulates Metabolic Networks Controlling Rapid Cell Growth and Proliferation

ABSTRACT: Rapidly proliferating cells reshape their metabolism to satisfy their ever-lasting need for building blocks. This phenomenon is exemplified in certain malignant conditions but also occurs during embryonic development, when cells rely heavily on glycolytic metabolism to exploit their metabolic intermediates for biosynthetic routes. How cells regulate this metabolic makeover is currently unknown. Here we report that loss of cathepsin L (CtsL) is associated with fast proliferation rate and enhanced glycolytic metabolism that depend on lactate dehydrogenase A (LDHA) activity. Furthermore, we show that CtsL inhibition led to increased LDHA expression, suggesting of a causal relationship between LDHA expression and function. In conclusion, we propose that CtsL regulate this metabolic circuit to keep cell division under check.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryo, Fibroblast

SUBMITTER: Farnusch Kaschani  

LAB HEAD: Farnusch Kaschani

PROVIDER: PXD011588 | Pride | 2019-05-06

REPOSITORIES: Pride