Constant growth rate can be supported by decreasing energy flux and increasing aerobic glycolysis

TY - JOUR

T1 - Constant growth rate can be supported by decreasing energy flux and increasing aerobic glycolysis

AU - Slavov, Nikolai

AU - Budnik, Bogdan A

AU - Schwab, David

AU - Airoldi, Edoardo M

AU - van Oudenaarden, Alexander

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014/5/8

Y1 - 2014/5/8

N2 - Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such roles in yeast batch cultures by quantifying O2 consumption, CO2 production, amino acids, mRNAs, proteins, posttranslational modifications, and stress sensitivity in the course of nine doublings at constant rate. During this course, the cells support a constant biomass-production rate with decreasing rates of respiration and ATP production but also decrease their stress resistance. As the respiration rate decreases, so do the levels of enzymes catalyzing rate-determining reactions of the tricarboxylic-acid cycle (providing NADH for respiration) and of mitochondrial folate-mediated NADPH production (required for oxidative defense). The findings demonstrate that exponential growth can represent not a single metabolic/physiological state but a continuum of changing states and that aerobic glycolysis can reduce the energy demands associated with respiratory metabolism and stress survival.

AB - Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such roles in yeast batch cultures by quantifying O2 consumption, CO2 production, amino acids, mRNAs, proteins, posttranslational modifications, and stress sensitivity in the course of nine doublings at constant rate. During this course, the cells support a constant biomass-production rate with decreasing rates of respiration and ATP production but also decrease their stress resistance. As the respiration rate decreases, so do the levels of enzymes catalyzing rate-determining reactions of the tricarboxylic-acid cycle (providing NADH for respiration) and of mitochondrial folate-mediated NADPH production (required for oxidative defense). The findings demonstrate that exponential growth can represent not a single metabolic/physiological state but a continuum of changing states and that aerobic glycolysis can reduce the energy demands associated with respiratory metabolism and stress survival.

KW - Adenosine Triphosphate

KW - Batch Cell Culture Techniques

KW - Biomass

KW - Citric Acid Cycle

KW - Energy Metabolism

KW - Glycolysis

KW - Mitochondria

KW - NADP

KW - Protein Processing, Post-Translational

KW - RNA, Messenger

KW - Saccharomyces cerevisiae

KW - Saccharomyces cerevisiae Proteins

KW - Transcription Factors

U2 - 10.1016/j.celrep.2014.03.057

DO - 10.1016/j.celrep.2014.03.057

M3 - Article

C2 - 24767987

SN - 2211-1247

VL - 7

SP - 705

EP - 714

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -