Functional and regulatory profiling of energy metabolism in fission yeast.

Michal Malecki,Graeme C Smith,Noelia Garcia Calavia,Maria Rodríguez-López,Jürg Bähler,Charalampos Rallis,Danny A Bitton

doi:10.1186/s13059-016-1101-2

Michal Malecki, Graeme C Smith + Show 5 more

Open Access

https://doi.org/10.1186/s13059-016-1101-2

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Abstract

BackgroundThe control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing. Metabolism in yeast cells can be manipulated by supplying different carbon sources: yeast grown on glucose rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration.ResultsWe screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. Growth media and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene-expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in energy metabolism pathways are coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that acetyl-CoA synthase, rather than citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction.ConclusionsThis study provides a rich framework of the genetic and regulatory basis of energy metabolism in fission yeast and beyond, and it pinpoints weaknesses of commonly used auxotroph mutants for investigating metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1101-2) contains supplementary material, which is available to authorized users.

Highlights

The control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing
Fission yeast uses mainly fermentation when grown in abundant glucose and respiration when grown on galactose or glycerol as carbon sources [24]
Two glucose-based growth media are commonly used for fission yeast: rich YES and minimal EMM media [27]

Summary

Introduction

The control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing. Glucose is a common source of energy for cells. Glucose metabolism starts with glycolysis, which produces pyruvate. Pyruvate can be metabolised by respiration via the mitochondrial tricarboxylic acid (TCA) cycle, called the Krebs or citric acid cycle [1, 2]. Electrons are transferred from NADH and other TCA products to oxygen through the electron transport chain (ETC), which generates a proton gradient across the mitochondrial membrane to produce ATP by oxidative phosphorylation (OXPHOS) [1, 2]. With respect to ATP production, respiration is much more efficient than

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