Mitochondria and cancer
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TLDR
Cancer cells then reprogramme adjacent stromal cells to optimize the cancer cell environment and activate out-of-context programmes that are important in development, stress response, wound healing and nutritional status.Abstract:
Contrary to conventional wisdom, functional mitochondria are essential for the cancer cell. Although mutations in mitochondrial genes are common in cancer cells, they do not inactivate mitochondrial energy metabolism but rather alter the mitochondrial bioenergetic and biosynthetic state. These states communicate with the nucleus through mitochondrial 'retrograde signalling' to modulate signal transduction pathways, transcriptional circuits and chromatin structure to meet the perceived mitochondrial and nuclear requirements of the cancer cell. Cancer cells then reprogramme adjacent stromal cells to optimize the cancer cell environment. These alterations activate out-of-context programmes that are important in development, stress response, wound healing and nutritional status.read more
Citations
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Journal ArticleDOI
Mitochondrial DNA Stress Primes the Antiviral Innate Immune Response
A. Phillip West,William Khoury-Hanold,Matthew M. Staron,Michal Caspi Tal,Cristiana M. Pineda,Sabine Lang,Megan Bestwick,Brett A. Duguay,Nuno Raimundo,Donna A. MacDuff,Susan M. Kaech,James R. Smiley,Robert E. Means,Akiko Iwasaki,Gerald S. Shadel +14 more
TL;DR: It is shown that moderate mtDNA stress elicited by TFAM deficiency engages cytosolic antiviral signalling to enhance the expression of a subset of interferon-stimulated genes, and it is suggested that cellular monitoring of mtDNA homeostasis cooperates with canonical virus sensing mechanisms to fully engage antiviral innate immunity.
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Targeting mitochondria metabolism for cancer therapy
TL;DR: Accumulating evidence now suggests that mitochondrial bioenergetics, biosynthesis and signaling are required for tumorigenesis, and emerging studies have begun to demonstrate that mitochondrial metabolism is potentially a fruitful arena for cancer therapy.
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Cancer metabolism: a therapeutic perspective
Ubaldo E. Martinez-Outschoorn,Maria Peiris-Pagès,Richard G. Pestell,Federica Sotgia,Federica Sotgia,Michael P. Lisanti +5 more
TL;DR: How cancer cells reprogramme their metabolism and that of other cells within the tumour microenvironment in order to survive and propagate, thus driving disease progression is discussed; in particular, potential metabolic vulnerabilities that might be targeted therapeutically are highlighted.
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The multifaceted roles of fatty acid synthesis in cancer
Florian Röhrig,Almut Schulze +1 more
TL;DR: This Review explores how different aspects of FA synthesis promote tumorigenesis and tumour progression and strategies to target this pathway have not yet translated into clinical practice.
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Acetyl Coenzyme A: A Central Metabolite and Second Messenger
TL;DR: By influencing the acetylation profile of several proteins, including histones, acetyl-CoA controls key cellular processes, including energy metabolism, mitosis, and autophagy, both directly and via the epigenetic regulation of gene expression.
References
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Journal ArticleDOI
Why do cancers have high aerobic glycolysis
TL;DR: In this article, the authors propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions, which leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity.
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The biology of cancer: metabolic reprogramming fuels cell growth and proliferation
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Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Lenny Dang,David W. White,Stefan Gross,Bryson D. Bennett,Mark A. Bittinger,Edward M. Driggers,Valeria Fantin,Hyun Gyung Jang,Shengfang Jin,Marie C. Keenan,Kevin Marks,Robert M. Prins,Patrick S. Ward,Katharine E. Yen,Linda M. Liau,Joshua D. Rabinowitz,Lewis C. Cantley,Craig B. Thompson,Matthew G. Vander Heiden,Matthew G. Vander Heiden,Shinsan M. Su +20 more
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A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine
TL;DR: The mitochondria provide a direct link between the authors' environment and their genes and the mtDNA variants that permitted their forbears to energetically adapt to their ancestral homes are influencing their health today.