Mitofusin-2 mediates doxorubicin sensitivity and acute resistance in Jurkat leukemia cells

Decker, Carl W.; Garcia, Jerome; Gatchalian, Kristelle; Arceneaux, Deronisha; Choi, Clarice; Cave, Si; Han, Derick; Hernandez, Jeniffer B.

doi:10.1016/j.bbrep.2020.100824

Cited by 15 publications

(12 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, upregulated OPA1 confers resistance to cytochrome c release upon prolonged venetoclax treatment in acute myeloid leukemia (AML) cells [ 118 ]. Consistently, upregulated MFN2 and increased OXPHOS have been found in cancer cells that survive chemotherapy [ 119 , 120 ]. Several other factors have been reported to promote cancer drug resistance by triggering mitochondrial fusion.…”

Section: Mitochondrial Stress Adaptation and Drug Resistancementioning

confidence: 68%

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

et al. 2022

View full text Add to dashboard Cite

Drug resistance represents a major obstacle in cancer management, and the mechanisms underlying stress adaptation of cancer cells in response to therapy-induced hostile environment are largely unknown. As the central organelle for cellular energy supply, mitochondria can rapidly undergo dynamic changes and integrate cellular signaling pathways to provide bioenergetic and biosynthetic flexibility for cancer cells, which contributes to multiple aspects of tumor characteristics, including drug resistance. Therefore, targeting mitochondria for cancer therapy and overcoming drug resistance has attracted increasing attention for various types of cancer. Multiple mitochondrial adaptation processes, including mitochondrial dynamics, mitochondrial metabolism, and mitochondrial apoptotic regulatory machinery, have been demonstrated to be potential targets. However, recent increasing insights into mitochondria have revealed the complexity of mitochondrial structure and functions, the elusive functions of mitochondria in tumor biology, and the targeting inaccessibility of mitochondria, which have posed challenges for the clinical application of mitochondrial-based cancer therapeutic strategies. Therefore, discovery of both novel mitochondria-targeting agents and innovative mitochondria-targeting approaches is urgently required. Here, we review the most recent literature to summarize the molecular mechanisms underlying mitochondrial stress adaptation and their intricate connection with cancer drug resistance. In addition, an overview of the emerging strategies to target mitochondria for effectively overcoming chemoresistance is highlighted, with an emphasis on drug repositioning and mitochondrial drug delivery approaches, which may accelerate the application of mitochondria-targeting compounds for cancer therapy.

show abstract

Section: Mitochondrial Stress Adaptation and Drug Resistancementioning

confidence: 68%

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

et al. 2022

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that venetoclax-resistant AML cells are also resistance to cytochrome c release whenever stimulated due to upregulation of OPA1 [458,459]. Since MFN2 deletion greatly enhances Jurkat doxorubicin sensitivity, MFN2 and OXPHOS have been discovered to be considerably elevated in surviving leukemia cells [460,461]. It has been discovered that suppressing MFN1 improves cisplatin sensitivity in human neuroblastoma cells by inhibiting mitochondrial fusion [462].…”

Section: Mitochondrial Fusion and Fissionmentioning

confidence: 99%

Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

Bahar

Han

Kim

et al. 2022

Cancers

View full text Add to dashboard Cite

Cancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. One of the well-known mechanisms of chemotherapy resistance is the change in the mitochondrial death pathways which occur when cells are under stressful situations, such as chemotherapy. Mitophagy, or mitochondrial selective autophagy, is critical for cell quality control because it can efficiently break down, remove, and recycle defective or damaged mitochondria. As cancer cells use mitophagy to rapidly sweep away damaged mitochondria in order to mediate their own drug resistance, it influences the efficacy of tumor chemotherapy as well as the degree of drug resistance. Yet despite the importance of mitochondria and mitophagy in chemotherapy resistance, little is known about the precise mechanisms involved. As a consequence, identifying potential therapeutic targets by analyzing the signal pathways that govern mitophagy has become a vital research goal. In this paper, we review recent advances in mitochondrial research, mitophagy control mechanisms, and their implications for our understanding of chemotherapy resistance.

show abstract

“…In particular, venetoclax-resistant AML cells show upregulation of OPA1, which likely establishes resistance to cytochrome c release upon stimulation [ 68 ]. In accordance with the role of mitochondrial fusion in chemoresistance, MFN2 and oxidative phosphorylation (OXPHOS) have been found to be significantly upregulated in surviving leukemia cells since the knockout of MFN2 substantially increases Jurkat sensitivity to doxorubicin [ 69 ]. In addition, it has been found that the inhibition of mitochondrial fusion by silencing MFN1 increases cisplatin sensitivity in human neuroblastoma cells [ 70 ].…”

Section: Role Of Mitochondrial Remodeling (Fusion Fission Mitophagy and Transfer) In Cancer Chemoresistancementioning

confidence: 99%

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Genovese

Carinci

Modesti

et al. 2021

IJMS

View full text Add to dashboard Cite

Mitochondria are key regulators of cell survival and are involved in a plethora of mechanisms, such as metabolism, Ca2+ signaling, reactive oxygen species (ROS) production, mitophagy and mitochondrial transfer, fusion, and fission (known as mitochondrial dynamics). The tuning of these processes in pathophysiological conditions is fundamental to the balance between cell death and survival. Indeed, ROS overproduction and mitochondrial Ca2+ overload are linked to the induction of apoptosis, while the impairment of mitochondrial dynamics and metabolism can have a double-faceted role in the decision between cell survival and death. Tumorigenesis involves an intricate series of cellular impairments not yet completely clarified, and a further level of complexity is added by the onset of apoptosis resistance mechanisms in cancer cells. In the majority of cases, cancer relapse or lack of responsiveness is related to the emergence of chemoresistance, which may be due to the cooperation of several cellular protection mechanisms, often mitochondria-related. With this review, we aim to critically report the current evidence on the relationship between mitochondria and cancer chemoresistance with a particular focus on the involvement of mitochondrial dynamics, mitochondrial Ca2+ signaling, oxidative stress, and metabolism to possibly identify new approaches or targets for overcoming cancer resistance.

show abstract

Mitofusin-2 mediates doxorubicin sensitivity and acute resistance in Jurkat leukemia cells

Cited by 15 publications

References 36 publications

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Contact Info

Product

Resources

About