Lactate Dehydrogenase B Controls Lysosome Activity and Autophagy in Cancer

Lucie Brisson (1) , Piotr Bański (1) , Martina Sboarina (1) , Coralie Dethier (1) , Pierre Danhier (1) , Marie-Joséphine Fontenille (1) , Vincent F van Hée (1) , Thibaut Vazeille (1) , Morgane Tardy (1) , Jorge Falces (1) , Caroline Bouzin (1) , Paolo Ettore Porporato (1) , Raphael Frederick (2) , Carine Michiels (3) , Tamara Copetti (1) , Pierre Sonveaux (1)

1 UCL - Université Catholique de Louvain = Catholic University of Louvain
2 LDRI - Louvain Drug Research Institute [Bruxelles, Belgique]
3 UNamur - Université de Namur [Namur]

Metabolic adaptability is essential for tumor progression and includes cooperation between cancer cells with different metabolic phenotypes. Optimal glucose supply to glycolytic cancer cells occurs when oxidative cancer cells use lactate preferentially to glucose. However, using lactate instead of glucose mimics glucose deprivation, and glucose starvation induces autophagy. We report that lactate sustains autophagy in cancer. In cancer cells preferentially to normal cells, lactate dehydrogenase B (LDHB), catalyzing the conversion of lactate and NAD+ to pyruvate, NADH and H+, controls lysosomal acidification, vesicle maturation, and intracellular proteolysis. LDHB activity is necessary for basal autophagy and cancer cell proliferation not only in oxidative cancer cells but also in glycolytic cancer cells.

Domaines: Cancer; Biologie cellulaire

Lucie Brisson, Piotr Bański, Martina Sboarina, Coralie Dethier, Pierre Danhier, et al.. Lactate Dehydrogenase B Controls Lysosome Activity and Autophagy in Cancer. Cancer Cell, 2016, 30 (3), pp.418 - 431. ⟨10.1016/j.ccell.2016.08.005⟩. ⟨hal-02908196⟩