scholarly journals Failure to Guard: Mitochondrial Protein Quality Control in Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8306
Author(s):  
Joseph E. Friedlander ◽  
Ning Shen ◽  
Aozhuo Zeng ◽  
Sovannarith Korm ◽  
Hui Feng
Keyword(s):  
Quality Control ◽  
Stress Responses ◽  
Surveillance System ◽  
Protein Quality ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Protein Quality Control ◽  
Mitochondrial Proteins ◽  
Anti Cancer ◽  
Key Pathways

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.

Protein quality control at the mitochondrion

2016 ◽  
Vol 60 (2) ◽  
pp. 213-225 ◽  
Author(s):  
Wolfgang Voos ◽  
Witold Jaworek ◽  
Anne Wilkening ◽  
Michael Bruderek
Keyword(s):  
Quality Control ◽  
Structural Integrity ◽  
Protein Quality ◽  
Mitochondrial Protein ◽  
Protein Quality Control ◽  
Eukaryotic Cell ◽  
Control Mechanisms ◽  
Biochemical Processes ◽  
Unfolded Protein ◽  
Protein Response

Mitochondria are essential constituents of a eukaryotic cell by supplying ATP and contributing to many mayor metabolic processes. As endosymbiotic organelles, they represent a cellular subcompartment exhibiting many autonomous functions, most importantly containing a complete endogenous machinery responsible for protein expression, folding and degradation. This article summarizes the biochemical processes and the enzymatic components that are responsible for maintaining mitochondrial protein homoeostasis. As mitochondria lack a large part of the required genetic information, most proteins are synthesized in the cytosol and imported into the organelle. After reaching their destination, polypeptides must fold and assemble into active proteins. Under pathological conditions, mitochondrial proteins become misfolded or damaged and need to be repaired with the help of molecular chaperones or eventually removed by specific proteases. Failure of these protein quality control mechanisms results in loss of mitochondrial function and structural integrity. Recently, novel mechanisms have been identified that support mitochondrial quality on the organellar level. A mitochondrial unfolded protein response allows the adaptation of chaperone and protease activities. Terminally damaged mitochondria may be removed by a variation of autophagy, termed mitophagy. An understanding of the role of protein quality control in mitochondria is highly relevant for many human pathologies, in particular neurodegenerative diseases.

Mitochondrial protein quality control: Implications in ageing

2008 ◽  
Vol 3 (6) ◽  
pp. 757-764 ◽  
Author(s):  
Bertrand Friguet ◽  
Anne-Laure Bulteau ◽  
Isabelle Petropoulos
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Mitochondrial Protein ◽  
Protein Quality Control

scholarly journals Mitochondrial Protein Quality Control: The Mechanisms Guarding Mitochondrial Health

2015 ◽  
Vol 22 (12) ◽  
pp. 977-994 ◽  
Author(s):  
Iryna Bohovych ◽  
Sherine S.L. Chan ◽  
Oleh Khalimonchuk
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Mitochondrial Protein ◽  
Protein Quality Control

scholarly journals Age-associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training

2012 ◽  
Vol 303 (2) ◽  
pp. R127-R134 ◽  
Author(s):  
Erika Koltai ◽  
Nikolett Hart ◽  
Albert W. Taylor ◽  
Sataro Goto ◽  
Jenny K. Ngo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Quality Control ◽  
Exercise Training ◽  
Mitochondrial Biogenesis ◽  
Protein Quality ◽  
Mitochondrial Protein ◽  
Protein Quality Control ◽  
Treadmill Running ◽  
Common Finding ◽  
Moderate Intensity

A decline in mitochondrial biogenesis and mitochondrial protein quality control in skeletal muscle is a common finding in aging, but exercise training has been suggested as a possible cure. In this report, we tested the hypothesis that moderate-intensity exercise training could prevent the age-associated deterioration in mitochondrial biogenesis in the gastrocnemius muscle of Wistar rats. Exercise training, consisting of treadmill running at 60% of the initial V̇o2max, reversed or attenuated significant age-associated (detrimental) declines in mitochondrial mass (succinate dehydrogenase, citrate synthase, cytochrome- c oxidase-4, mtDNA), SIRT1 activity, AMPK, pAMPK, and peroxisome proliferator-activated receptor gamma coactivator 1-α, UCP3, and the Lon protease. Exercise training also decreased the gap between young and old animals in other measured parameters, including nuclear respiratory factor 1, mitochondrial transcription factor A, fission-1, mitofusin-1, and polynucleotide phosphorylase levels. We conclude that exercise training can help minimize detrimental skeletal muscle aging deficits by improving mitochondrial protein quality control and biogenesis.

The role of protein quality control in mitochondrial protein homeostasis under oxidative stress

PROTEOMICS ◽  
2010 ◽  
Vol 10 (7) ◽  
pp. 1426-1443 ◽  
Author(s):  
Tom Bender ◽  
Claudia Leidhold ◽  
Thomas Ruppert ◽  
Sebastian Franken ◽  
Wolfgang Voos
Keyword(s):  
Oxidative Stress ◽  
Quality Control ◽  
Protein Quality ◽  
Mitochondrial Protein ◽  
Protein Quality Control ◽  
Protein Homeostasis

Increasing organismal healthspan by enhancing mitochondrial protein quality control

2009 ◽  
Vol 11 (7) ◽  
pp. 852-858 ◽  
Author(s):  
Karin Luce ◽  
Heinz D. Osiewacz
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Mitochondrial Protein ◽  
Protein Quality Control

Linking mitochondrial dynamics to mitochondrial protein quality control

2016 ◽  
Vol 38 ◽  
pp. 68-74 ◽  
Author(s):  
Suraiya Haroon ◽  
Marc Vermulst
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Protein ◽  
Protein Quality Control

scholarly journals Clearing Traffic Jams During Protein Translocation Across Membranes

2021 ◽  
Vol 8 ◽  
Author(s):  
Lihui Wang ◽  
Yihong Ye
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Lipid Bilayers ◽  
Protein Quality ◽  
Protein Translocation ◽  
Control Strategies ◽  
Protein Quality Control ◽  
Traffic Jams ◽  
Protein Biogenesis

Protein translocation across membranes is a critical facet of protein biogenesis in compartmentalized cells as proteins synthesized in the cytoplasm often need to traverse across lipid bilayers via proteinaceous channels to reach their final destinations. It is well established that protein biogenesis is tightly linked to various protein quality control processes, which monitor errors in protein folding, modification, and localization. However, little is known about how cells cope with translocation defective polypeptides that clog translocation channels (translocons) during protein translocation. This review summarizes recent studies, which collectively reveal a set of translocon-associated quality control strategies for eliminating polypeptides stuck in protein-conducting channels in the endoplasmic reticulum and mitochondria.

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