TY - JOUR
T1 - Mitochondrial dysfunctions in cancer
T2 - Genetic defects and oncogenic signaling impinging on TCA cycle activity
AU - Desideri, Enrico
AU - Vegliante, Rolando
AU - Ciriolo, Maria Rosa
PY - 2015/1/28
Y1 - 2015/1/28
N2 - The tricarboxylic acid (TCA) cycle is a central route for oxidative metabolism. Besides being responsible for the production of NADH and FADH2, which fuel the mitochondrial electron transport chain to generate ATP, the TCA cycle is also a robust source of metabolic intermediates required for anabolic reactions. This is particularly important for highly proliferating cells, like tumour cells, which require a continuous supply of precursors for the synthesis of lipids, proteins and nucleic acids. A number of mutations among the TCA cycle enzymes have been discovered and their association with some tumour types has been established. In this review we summarise the current knowledge regarding alterations of the TCA cycle in tumours, with particular attention to the three germline mutations of the enzymes succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase, which are involved in the pathogenesis of tumours, and to the aberrant regulation of TCA cycle components that are under the control of oncogenes and tumour suppressors.
AB - The tricarboxylic acid (TCA) cycle is a central route for oxidative metabolism. Besides being responsible for the production of NADH and FADH2, which fuel the mitochondrial electron transport chain to generate ATP, the TCA cycle is also a robust source of metabolic intermediates required for anabolic reactions. This is particularly important for highly proliferating cells, like tumour cells, which require a continuous supply of precursors for the synthesis of lipids, proteins and nucleic acids. A number of mutations among the TCA cycle enzymes have been discovered and their association with some tumour types has been established. In this review we summarise the current knowledge regarding alterations of the TCA cycle in tumours, with particular attention to the three germline mutations of the enzymes succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase, which are involved in the pathogenesis of tumours, and to the aberrant regulation of TCA cycle components that are under the control of oncogenes and tumour suppressors.
KW - Aconitase
KW - Fumarate hydratase
KW - HIF
KW - Isocitrate dehydrogenase
KW - P53
KW - Succinate dehydrogenase
UR - http://www.scopus.com/inward/record.url?scp=84920136325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920136325&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2014.02.023
DO - 10.1016/j.canlet.2014.02.023
M3 - Article
C2 - 24614286
AN - SCOPUS:84920136325
VL - 356
SP - 217
EP - 223
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 2
ER -