Failure to Guard: Mitochondrial Protein Quality Control in Cancer

Author:

Friedlander Joseph E.,Shen Ning,Zeng Aozhuo,Korm SovannarithORCID,Feng HuiORCID

Abstract

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.

Funder

National Cancer Institute

National Institutes of Health

National Science Foundation

American Cancer Society

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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