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Title: Failure to Guard: Mitochondrial Protein Quality Control in Cancer
Mitochondria are energetic and dynamic organelles with a crucial role in bioenergetics, metabolism, and signaling. Mitochondrial proteins, encoded by both nuclear and mitochondrial DNA, must be properly regulated to ensure proteostasis. Mitochondrial protein quality control (MPQC) serves as a critical surveillance system, employing different pathways and regulators as cellular guardians to ensure mitochondrial protein quality and quantity. In this review, we describe key pathways and players in MPQC, such as mitochondrial protein translocation-associated degradation, mitochondrial stress responses, chaperones, and proteases, and how they work together to safeguard mitochondrial health and integrity. Deregulated MPQC leads to proteotoxicity and dysfunctional mitochondria, which contributes to numerous human diseases, including cancer. We discuss how alterations in MPQC components are linked to tumorigenesis, whether they act as drivers, suppressors, or both. Finally, we summarize recent advances that seek to target these alterations for the development of anti-cancer drugs.  more » « less
Award ID(s):
1911253
NSF-PAR ID:
10341687
Author(s) / Creator(s):
; ; ; ;
Date Published:
Journal Name:
International Journal of Molecular Sciences
Volume:
22
Issue:
15
ISSN:
1422-0067
Page Range / eLocation ID:
8306
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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