Regulation of Mitochondrial Function by the Actin Cytoskeleton

Illescas, M. E. Banegas; Peñas, Ana; Arenas, Joaquín; Martín, Miguel; Ugalde, Cristina

doi:10.3389/fcell.2021.795838

Cited by 41 publications

(27 citation statements)

References 127 publications

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“…Furthermore, our data demonstrated that the F-actin stabilizer jasplakinolide alleviates βII spectrin de ciency-induced mitochondrial dysfunction and apoptosis, suggesting that βII spectrin regulates mitochondrial function by stabilizing F-actin. It has been established that F-actin localizes to mitochondria 40 . Most previous studies on the regulation of mitochondrial function by F-actin have focused on F-actin localization outside mitochondria to mediate mitochondrial dynamics 41,42 , tra cking and autophagy 43 .…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Cardiomyocyte βII Spectrin Plays a Critical Role in Maintaining Cardiac Function via Regulating Mitochondrial Respiratory Function

Wang

Yang

Ruan

et al. 2022

Preprint

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βII spectrin is a cytoskeletal protein known to be tightly linked to heart development and cardiovascular electrophysiology. However, roles of βII spectrin in cardiac contractile function and post-myocardial infarction pathological remodeling remain unclear. Here, we uncovered that the levels of serum βII spectrin breakdown products (βII SBDPs) were significantly increased in patients with acute myocardial infarction. Consistently, βII spectrin was degraded into βII SBDPs by calpain in mouse hearts after ischemia/reperfusion (I/R) injury. Cardiac-specific βII spectrin deletion results in spontaneous development of cardiac contractile dysfunction, cardiac hypertrophy and fibrosis. Moreover, deletion of βII spectrin in the adult heart exacerbated I/R-induced cardiomyocyte death and heart failure, while restoration of βII spectrin expression by adenoviral saRNA delivery in the heart reduced I/R injury. IP–LC–MS/MS and functional studies revealed that βII spectrin is indispensable for mitochondrial complex I activity and respiratory function. Mechanistically, βII spectrin interacted with mitochondrial complex I to mediate its assembly by crosslinking with actin filaments (F-actin) to maintain F-actin stability. These findings identify βII spectrin as an essential mitochondrial cytoskeletal element for preserving mitochondrial homeostasis and cardiac function.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Cardiomyocyte βII Spectrin Plays a Critical Role in Maintaining Cardiac Function via Regulating Mitochondrial Respiratory Function

Wang

Yang

Ruan

et al. 2022

Preprint

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show abstract

“…TQ significantly increased the expression of ACTB and BAG1 in both cell lines. Perhaps beta-actin helps to initiate apoptosis by allowing cytosolic pro-apoptotic proteins to be carried to mitochondria by a cytoskeleton-driven trafficking system [ 124 ]. Previous research has shown that actin can be used as a substrate for caspase cleavage in mammalian cells [ 125 ].…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

et al. 2022

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Breast cancer (BC) is the most common cancer in women worldwide, and it is one of the leading causes of cancer death in women. triple-negative breast Cancer (TNBC), a subtype of BC, is typically associated with the highest pathogenic grade and incidence in premenopausal and young African American (AA) women. Chemotherapy, the most common treatment for TNBC today, can lead to acquired resistance and ineffective treatment. Therefore, novel therapeutic approaches are needed to combat medication resistance and ineffectiveness in TNBC patients. Thymoquinone (TQ) is shown to have a cytotoxic effect on human cancer cells in vitro. However, TQ’s mode of action and precise mechanism in TNBC disease in vitro have not been adequately investigated. Therefore, TQ’s effects on the genetically different MDA-MB-468 and MDA-MB-231 human breast cancer cell lines were assessed. The data obtained show that TQ displayed cytotoxic effects on MDA-MB-468 and MDA-MB-231 cells in a time- and concentration-dependent manner after 24 h, with IC50 values of 25.37 µM and 27.39 µM, respectively. Moreover, MDA-MB-231 and MDA-MB-468 cells in a scratched wound-healing assay displayed poor wound closure, inhibiting invasion and migration via cell cycle blocking after 24 h. TQ arrested the cell cycle phase in MDA-MB-231 and MDA-MB-468 cells. The three cell cycle stages in MDA-MB-468 cells were significantly affected at 15 and 20 µM for G0/G1 and S phases, as well as all TQ concentrations for G2/M phases. In MDA-MB-468 cells, there was a significant decrease in G0/G1 phases with a substantial increase in the S phase and G2/M phases. In contrast, MDA-MB-231 showed a significant effect only during the two cell cycle stages (S and G2/M), at concentrations of 15 and 20 µM for S phases and all TQ values for G2/M phases. The TQ effect on the apoptotic gene profiles indicated that TQ upregulated 15 apoptotic genes in MDA-MB-231 TNBC cells, including caspases, GADD45A, TP53, DFFA, DIABLO, BNIP3, TRAF2/3, and TNFRSF10A. In MDA-MB-468 cells, 16 apoptotic genes were upregulated, including TNFRSF10A, TNF, TNFRSF11B, FADD TNFRSF10B, CASP2, and TRAF2, all of which are important for the apoptotic pathway andsuppress the expression of one anti-apoptotic gene, BIRC5, in MDA-MB-231 cells. Compared to MDA-MB-231 cells, elevated levels of TNF and their receptor proteins may contribute to their increased sensitivity to TQ-induced apoptosis. It was concluded from this study that TQ targets the MDA-MB-231 and MDA-MB-468 cells differently. Additionally, due to the aggressive nature of TNBC and the lack of specific therapies in chemoresistant TNBC, our findings related to the identified apoptotic gene profile may point to TQ as a potential agent for TNBC therapy.

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“…MtDNAs have historically been assumed to be selectively neutral (Galtier et al, 2009 ; Immonen et al, 2020 ). However, accumulating information shows that this molecule may be under strong selection for ecological adaptation (Zhan et al, 2004 ; Immonen et al, 2020 ), consistent with its involvement in the differentiation, information transmission and apoptosis of cells (Scheckhuber et al, 2007 ), regulation of body biomass (Illescas et al, 2021 ), response to environmental stresses such as pathogen resistance to host immunity (Bartelli et al, 2018 ) and pesticides, and we believe that natural selection for local adaptation also contributes to the spatial distribution of mtDNA observed in P. infestans . Our argument is supported by several lines of evidence as listed below.…”

Section: Discussionmentioning

confidence: 80%

Mitochondrial Genome Contributes to the Thermal Adaptation of the Oomycete Phytophthora infestans

et al. 2022

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As a vital element of climate change, elevated temperatures resulting from global warming present new challenges to natural and agricultural sustainability, such as ecological disease management. Mitochondria regulate the energy production of cells in responding to environmental fluctuation, but studying their contribution to the thermal adaptation of species is limited. This knowledge is needed to predict future disease epidemiology for ecology conservation and food security. Spatial distributions of the mitochondrial genome (mtDNA) in 405 Phytophthora infestans isolates originating from 15 locations were characterized. The contribution of MtDNA to thermal adaptation was evaluated by comparative analysis of mtDNA frequency and intrinsic growth rate, relative population differentiation in nuclear and mtDNA, and associations of mtDNA distribution with local geography climate conditions. Significant variation in frequency, intrinsic growth rate, and spatial distribution was detected in mtDNA. Population differentiation in mtDNA was significantly higher than that in the nuclear genome, and spatial distribution of mtDNA was strongly associated with local climatic conditions and geographic parameters, particularly air temperature, suggesting natural selection caused by a local temperature is the main driver of the adaptation. Dominant mtDNA grew faster than the less frequent mtDNA. Our results provide useful insights into the evolution of pathogens under global warming. Given its important role in biological functions and adaptation to local air temperature, mtDNA intervention has become an increasing necessity for future disease management. To secure ecological integrity and food production under global warming, a synergistic study on the interactive effect of changing temperature on various components of biological and ecological functions of mitochondria in an evolutionary frame is urgently needed.

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Regulation of Mitochondrial Function by the Actin Cytoskeleton

Cited by 41 publications

References 127 publications

WITHDRAWN: Cardiomyocyte βII Spectrin Plays a Critical Role in Maintaining Cardiac Function via Regulating Mitochondrial Respiratory Function

WITHDRAWN: Cardiomyocyte βII Spectrin Plays a Critical Role in Maintaining Cardiac Function via Regulating Mitochondrial Respiratory Function

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

Mitochondrial Genome Contributes to the Thermal Adaptation of the Oomycete Phytophthora infestans

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