Increased mitochondrial fission promotes autophagy and hepatocellular carcinoma cell survival through the ROS-modulated coordinated regulation of the NFKB and TP53 pathways.
Citations
351 citations
Cites background from "Increased mitochondrial fission pro..."
...Besides, fission can be induced by ROS via the Akt- and NFκB-pathway [49]....
[...]
323 citations
Cites background from "Increased mitochondrial fission pro..."
...Promisingly, mdivi-1, an allosteric and reversible Drp1 inhibitor, induced apoptosis and suppressed the growth of xenograft HCC tumors in immunodeficient mouse model [208]....
[...]
...Increased mitochondrial fragmentation corresponded to an unfavorable prognosis for hepatocellular carcinoma (HCC) patients presumably due to concurrent Drp1 upregulation and downregulation of Mfn1 [208]....
[...]
...Mechanistically, mitochondrial fission-induced redox activation of Akt promoted Mdm2-dependent ubiquitin-proteasomal degradation of p53 and IKK-dependent NF-κB activation [208]....
[...]
...The fragmented mitochondrial phenotype observed after Drp1 overexpression or Mfn1 knockdown in several HCC cell lines was associated with ROS overproduction, Akt (also known as protein kinase B) activation, evasion of apoptosis, and induction of general autophagy pathway [208]....
[...]
233 citations
166 citations
139 citations
Cites background from "Increased mitochondrial fission pro..."
...An increased mitochondrial fission significantly promotes HCC cell survival by increasing autophagy and resistance to apoptosis.(56) ROS production is also increased by this mitochondrial process, leading to upregulation of BECN1, ROS-induced AKT activation, and modulation of TP53 and NFKB pathways....
[...]
...Worthy of note, in HCC mitochondrial fission, is frequently increased and contributes to poor prognosis.(56) Autophagy appears to assume a pro-survival (tumorpromoting) function once HCC is established, and an increased autophagy flux has been found to correlate with malignant progression and poor prognosis of this cancer(57) (see also section titled p62-Nrf2 and other autophagyrelated proteins in the clinical monitoring of HCC and Table I)....
[...]
References
3,002 citations
"Increased mitochondrial fission pro..." refers background in this paper
...A series of studies have demonstrated that autophagy can protect cells by preventing them from apoptosis.(17,18) We thus clarified whether autophagy plays a critical role in mitochondrial fission-mediated inhibition of HCC cell apoptosis....
[...]
2,642 citations
"Increased mitochondrial fission pro..." refers background in this paper
...A body of evidence has indicated that mitochondrial fission appears to be a prerequisite for mitophagy both in mammal and yeast cells.(12,30) Moreover, mitochondrial fission is important in mediating global autophagy in cardiomyocytes under glucose deprivation,(11) which protects heart cells against energy stress....
[...]
...However, several studies in mouse embryonic fibroblasts and insulinoma b-cells also indicate that inhibition of mitochondrial fission only results in reduction of mitophagy but not nonspecific global autophagy.(12,32) We speculated that, under cellular stresses, such as glucose deprivation or tumorigenesis, mitochondrial fission is more likely to induce a consistent constitutive global autophagy to promoted cell survival by degrading redundant or damaged proteins and organelles....
[...]
2,169 citations
1,835 citations
"Increased mitochondrial fission pro..." refers background in this paper
...The dynamic nature of mitochondrial network is thought to be important for intermixing of DNA and proteins between mitochondria and for rapid repair of damaged mitochondria.(2)...
[...]
1,637 citations
"Increased mitochondrial fission pro..." refers background in this paper
...Highly conserved dynamin-related GTPases have been identified as the primary regulators of mitochondrial dynamics.(1) Notably,...
[...]
...Morphologically, the mitochondrial network exists as mixed structures of long interconnected tubules with short isolated dot-like spheres, which is precisely regulated by 2 opposing processes: fusion and fission.(1) Highly conserved dynamin-related GTPases have been identified as the primary regulators of mitochondrial dynamics....
[...]