The mitochondrial unfolded protein response (UPRmt): shielding against toxicity to mitochondria in cancer

Mitochondria are essential for tumor growth and progression. However, the heavy demand for mitochondrial activity in cancer leads to increased production of mitochondrial reactive oxygen species (mtROS), accumulation of mutations in mitochondrial DNA, and development of mitochondrial dysfunction. If...

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Bibliographic Details
Published in:Journal of hematology and oncology 2022-07, Vol.15 (1), p.1-98, Article 98
Main Authors: Inigo, Joseph R, Chandra, Dhyan
Format: Article
Language:English
Subjects:
Addictions
Cancer
Cell growth
Cyclin-dependent kinases
Dehydrogenases
Enzymes
Genes
Hematology
Hydrogen peroxide
Kinases
Mammals
Mitochondria
Mitochondrial chaperonins
Mitochondrial DNA
Mitochondrial proteases
Mitochondrial proteostasis
Mitochondrial unfolded protein response
Mutation
Oncology
Oxidative stress
Proteases
Protein folding
Proteins
Quality control
Reactive oxygen species
Review
Sarcoma
Telecommunication systems
Toxicity
Tumorigenesis
Tumors
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Summary:Mitochondria are essential for tumor growth and progression. However, the heavy demand for mitochondrial activity in cancer leads to increased production of mitochondrial reactive oxygen species (mtROS), accumulation of mutations in mitochondrial DNA, and development of mitochondrial dysfunction. If left unchecked, excessive mtROS can damage and unfold proteins in the mitochondria to an extent that becomes lethal to the tumor. Cellular systems have evolved to combat mtROS and alleviate mitochondrial stress through a quality control mechanism called the mitochondrial unfolded protein response (UPR.sup.mt). The UPR.sup.mt system is composed of chaperones and proteases, which promote protein folding or eliminate mitochondrial proteins damaged by mtROS, respectively. UPR.sup.mt is conserved and activated in cancer in response to mitochondrial stress to maintain mitochondrial integrity and support tumor growth. In this review, we discuss how mitochondria become dysfunctional in cancer and highlight the tumor-promoting functions of key components of the UPR.sup.mt. Keywords: Mitochondrial unfolded protein response, Mitochondrial chaperonins, Mitochondrial proteases, Mitochondrial proteostasis, Cancer
ISSN:1756-8722
1756-8722
DOI:10.1186/s13045-022-01317-0