Lactate Dehydrogenase B Controls Lysosome Activity and Autophagy in Cancer.
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.
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Lucie
L
Brisson
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Piotr
P
Bański
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Martina
M
Sboarina
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Coralie
C
Dethier
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium; Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Pierre
P
Danhier
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Marie-Joséphine
MJ
Fontenille
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Vincent F
VF
Van Hée
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Thibaut
T
Vazeille
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Morgane
M
Tardy
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Jorge
J
Falces
IREC Imaging Platform, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Caroline
C
Bouzin
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Paolo E
PE
Porporato
Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Raphaël
R
Frédérick
URBC-NARILIS, University of Namur, 5000 Namur, Belgium.
Carine
C
Michiels
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium.
Tamara
T
Copetti
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université catholique de Louvain (UCL), 1200 Brussels, Belgium. Electronic address: pierre.sonveaux@uclouvain.be.
Pierre
P
Sonveaux
D000818:Animals; D001343:Autophagy / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*
D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1