TY - JOUR
T1 - The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria
AU - Xu, Wanting
AU - Dong, Lei
AU - Dai, Ji
AU - Zhong, Lu
AU - Ouyang, Xiao
AU - Li, Jiaqian
AU - Feng, Gaoqing
AU - Wang, Huahua
AU - Liu, Xuan
AU - Zhou, Liying
AU - Xia, Qin
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Uncontrollable cancer cell growth is characterized by the maintenance of cellular homeostasis through the continuous accumulation of misfolded proteins and damaged organelles. This review delineates the roles of two complementary and synergistic degradation systems, the ubiquitin–proteasome system (UPS) and the autophagy-lysosome system, in the degradation of misfolded proteins and damaged organelles for intracellular recycling. We emphasize the interconnected decision-making processes of degradation systems in maintaining cellular homeostasis, such as the biophysical state of substrates, receptor oligomerization potentials (e.g., p62), and compartmentalization capacities (e.g., membrane structures). Mitochondria, the cellular hubs for respiration and metabolism, are implicated in tumorigenesis. In the subsequent sections, we thoroughly examine the mechanisms of mitochondrial quality control (MQC) in preserving mitochondrial homeostasis in human cells. Notably, we explored the relationships between mitochondrial dynamics (fusion and fission) and various MQC processes—including the UPS, mitochondrial proteases, and mitophagy—in the context of mitochondrial repair and degradation pathways. Finally, we assessed the potential of targeting MQC (including UPS, mitochondrial molecular chaperones, mitochondrial proteases, mitochondrial dynamics, mitophagy and mitochondrial biogenesis) as cancer therapeutic strategies. Understanding the mechanisms underlying mitochondrial homeostasis may offer novel insights for future cancer therapies.
AB - Uncontrollable cancer cell growth is characterized by the maintenance of cellular homeostasis through the continuous accumulation of misfolded proteins and damaged organelles. This review delineates the roles of two complementary and synergistic degradation systems, the ubiquitin–proteasome system (UPS) and the autophagy-lysosome system, in the degradation of misfolded proteins and damaged organelles for intracellular recycling. We emphasize the interconnected decision-making processes of degradation systems in maintaining cellular homeostasis, such as the biophysical state of substrates, receptor oligomerization potentials (e.g., p62), and compartmentalization capacities (e.g., membrane structures). Mitochondria, the cellular hubs for respiration and metabolism, are implicated in tumorigenesis. In the subsequent sections, we thoroughly examine the mechanisms of mitochondrial quality control (MQC) in preserving mitochondrial homeostasis in human cells. Notably, we explored the relationships between mitochondrial dynamics (fusion and fission) and various MQC processes—including the UPS, mitochondrial proteases, and mitophagy—in the context of mitochondrial repair and degradation pathways. Finally, we assessed the potential of targeting MQC (including UPS, mitochondrial molecular chaperones, mitochondrial proteases, mitochondrial dynamics, mitophagy and mitochondrial biogenesis) as cancer therapeutic strategies. Understanding the mechanisms underlying mitochondrial homeostasis may offer novel insights for future cancer therapies.
KW - Autophagy-lysosome
KW - Cancer therapy
KW - Mitochondrial chaperones
KW - Mitochondrial proteases
KW - Mitophagy
KW - Protein quality control
KW - UPS
UR - http://www.scopus.com/inward/record.url?scp=85215355422&partnerID=8YFLogxK
U2 - 10.1007/s00018-024-05556-x
DO - 10.1007/s00018-024-05556-x
M3 - Review article
C2 - 39800773
AN - SCOPUS:85215355422
SN - 1420-682X
VL - 82
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 1
M1 - 42
ER -