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Cancer and Metabolism

, 3:1

First Online: 25 January 2015Received: 29 September 2014Accepted: 02 January 2015DOI: 10.1186-s40170-015-0128-2

Cite this article as: Ahn, C.S. & Metallo, C.M. Cancer Metab 2015 3: 1. doi:10.1186-s40170-015-0128-2

Abstract

Unchecked growth and proliferation is a hallmark of cancer, and numerous oncogenic mutations reprogram cellular metabolism to fuel these processes. As a central metabolic organelle, mitochondria execute critical biochemical functions for the synthesis of fundamental cellular components, including fatty acids, amino acids, and nucleotides. Despite the extensive interest in the glycolytic phenotype of many cancer cells, tumors contain fully functional mitochondria that support proliferation and survival. Furthermore, tumor cells commonly increase flux through one or more mitochondrial pathways, and pharmacological inhibition of mitochondrial metabolism is emerging as a potential therapeutic strategy in some cancers. Here, we review the biosynthetic roles of mitochondrial metabolism in tumors and highlight specific cancers where these processes are activated.

KeywordsCancer Mitochondria Biosynthesis Amino acids Nucleotides Anaplerosis Lipogenesis AbbreviationsFDG2-deoxy-2- Ffluoro-D-glucose

CH2-THF5,10-methylene tetrahydrofolate

10-CHO-THF10-formyl-tetrahydrofolate

ATPadenosine triphosphate

GOTaspartate transaminases

ASNSasparagine synthetase

AMLacute myeloblastic leukemia

AcCoAacetyl-coenzyme A

Alaalanine

GPTalanine transaminases

aKGalpha-ketoglutarate

BCATbranched chain aminotransferase

Citcitrate

cALLchildhood acute lymphoblastic leukemia

P5CSdelta-1-pyrroline-5-carboxylate synthase

DHODHdihydroorotate dehydrogenase

ETCelectron transport chain

EGFepidermal growth factor

FOCMfolate-mediated one carbon metabolism

Fumfumarate

FHfumarate hydratase

Glnglutamine

Gluglutamate

Glyglycine

GSglutamine synthetase

GLSglutaminase

GDHglutamate dehydrogenase

HOTshuman orthotopic tumors

HIFhypoxia inducible factor

ICTisocitrate

IDHisocitrate dehydrogenase

Laclactate

LKB1liver kinase B1

MSmass spectrometry

mTORC1mammalian target of rapamycin complex 1

MEmalic enzymes

Malmalate

MTHFDmethylenetetrahydrofolate dehydrogenase

NADHnicotinamide adenine dinucleotide, reduced

NADPHnicotinamide adenine dinucleotide phosphate, reduced

NNTnicotinamide nucleotide transhydrogenase

NMRnuclear magnetic resonance

OACoxaloacetate

PET-CTpositron emission tomography integrated with computed tomography

PDACpancreatic adenocarcinoma

Pyrpyruvate

PDHpyruvate dehydrogenase

PCpyruvate carboxylase

PDKPDH kinase

P5Cpyrroline-5-carboxylate

PYCRpyrroline-5-carboxylate reductase

POXproline oxidase

ROSreactive oxygen species

Serserine

SHMTserine hydroxymethyltransferase

SREBP1sterol regulatory element binding protein 1

Sucsuccinate

SDHsuccinate dehydrogenase

TCAtricarboxylic acid

TRAILtumor necrosis factor-related apoptosis-inducing ligand

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Author: Christopher S Ahn - Christian M Metallo

Source: https://link.springer.com/







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