Increased mitochondrial fission promotes autophagy and hepatocellular carcinoma cell survival through the ROS-modulated coordinated regulation of the NFKB and TP53 pathways.
Qichao Huang,Lei Zhan,Haiyan Cao,Jibin Li,Yinghua Lyu,Xu Guo,Jing Zhang,Lele Ji,Tingting Ren,Jiaze An,Bingrong Liu,Yongzhan Nie,Jinliang Xing +12 more
Reads0
Chats0
TLDR
It is demonstrated that increased mitochondrial fission plays a critical role in regulation of HCC cell survival, which provides a strong evidence for this process as drug target in HCC treatment.Abstract:
Mitochondrial morphology is dynamically remodeled by fusion and fission in cells, and dysregulation of this process is closely implicated in tumorigenesis. However, the mechanism by which mitochondrial dynamics influence cancer cell survival is considerably less clear, especially in hepatocellular carcinoma (HCC). In this study, we systematically investigated the alteration of mitochondrial dynamics and its functional role in the regulation of autophagy and HCC cell survival. Furthermore, the underlying molecular mechanisms and therapeutic application were explored in depth. Mitochondrial fission was frequently upregulated in HCC tissues mainly due to an elevated expression ratio of DNM1L to MFN1, which significantly contributed to poor prognosis of HCC patients. Increased mitochondrial fission by forced expression of DNM1L or knockdown of MFN1 promoted the survival of HCC cells both in vitro and in vivo mainly by facilitating autophagy and inhibiting mitochondria-dependent apoptosis. We further demonstrated that the survival-promoting role of increased mitochondrial fission was mediated via elevated ROS production and subsequent activation of AKT, which facilitated MDM2-mediated TP53 degradation, and NFKBIA- and IKK-mediated transcriptional activity of NFKB in HCC cells. Also, a crosstalk between TP53 and NFKB pathways was involved in the regulation of mitochondrial fission-mediated cell survival. Moreover, treatment with mitochondrial division inhibitor-1 significantly suppressed tumor growth in an in vivo xenograft nude mice model. Our findings demonstrate that increased mitochondrial fission plays a critical role in regulation of HCC cell survival, which provides a strong evidence for this process as drug target in HCC treatment.read more
Citations
More filters
Journal ArticleDOI
Antioxidant Supplementation
TL;DR: In this paper , it has been observed that the antioxidants may alter chemotherapy by scavenging reactive oxygen species in the cell and also the time duration from chemotherapy is also a factor for improved compliance towards chemotherapy as it may decrease the level of associated side effects.
Journal ArticleDOI
Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction
Mahesh Ramalingam,Su Jeong Jang,Jinsu Hwang,Boeun Kim,Hyong-Ho Cho,Eung-Suk Kim,Han-Seong Jeong +6 more
TL;DR: In this article , the authors examined the neuroprotective effects of the secretome from neural-induced human adipose tissue-derived stem cells (NI-ADSC-SM) during ROT toxicity in SH-SY5Y cells.
Journal ArticleDOI
Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity
Min Jiang,Zifan Liu,Junjie Shao,Jingjing Zhou,Haiming Wang,Chao Song,Xin Li,Lin Wang,Qiang Xu,Xiaojuan Liu,Le-Jian Lin,Ran Zhang +11 more
TL;DR: In this paper , the authors investigated whether estrogen receptor α (ERα)-NRF1-OMI-mitophagy signaling was involved in the dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) under simulated microgravity.
Journal ArticleDOI
Mitochondrial Control in Inflammatory Gastrointestinal Diseases
TL;DR: In this article , the authors focus on the mitochondria and inflammatory signaling pathways and its related gastrointestinal diseases and show that mitochondria dysfunction in the gastrointestinal system leads to the excessive activation of multiple inflammatory signalling pathways, leading to IBD and increased severity of colorectal cancer.
Journal ArticleDOI
ICD-related risk model predicts the prognosis and immunotherapy response of patients with liver cancer
TL;DR: In this paper , three ICD-related prognostic genes, the prion protein gene (PRNP), dynamin 1-like gene (DNM1L), and caspase-8 (CASP8), were identified and used to construct a risk signature.
References
More filters
Journal ArticleDOI
Autophagy and the Integrated Stress Response
TL;DR: Autophagy is a cell biological process that is a central component of the integrated stress response and can be integrated with other cellular stress responses through parallel stimulation of autophagy and other stress responses by specific stress stimuli.
Journal ArticleDOI
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Gilad Twig,Alvaro A. Elorza,Anthony J.A. Molina,Anthony J.A. Molina,Hibo Mohamed,Jakob D. Wikstrom,Gil Walzer,Linsey Stiles,Sarah E. Haigh,Steve Katz,Guy Las,Joseph Alroy,Min Wu,Bénédicte F. Py,Junying Yuan,Jude T. Deeney,Barbara E. Corkey,Orian S. Shirihai +17 more
TL;DR: Pulse chase and arrest of autophagy at the pre‐proteolysis stage reveal that fission followed by selective fusion segregates dysfunctional mitochondria and permits their removal by autophagic.
Journal ArticleDOI
Integrating cell-signalling pathways with NF-kappaB and IKK function.
TL;DR: This work has shown that crosstalk constitutes a decision-making process that determines the consequences of NF-κB and IKK activation and, ultimately, cell fate.
Journal ArticleDOI
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
TL;DR: Recent work is discussed that suggests that the dynamics (fusion and fission) of these organelles is important in development and disease.
Journal ArticleDOI
Mitochondrial fusion and fission in cell life and death
TL;DR: The core components of the evolutionarily conserved fusion and fission machineries have now been identified, and mechanistic studies have revealed the first secrets of the complex processes that govern fusion andfission of a double membrane-bound organelle.