Mitochondrial matrix-localized Src kinase regulates mitochondrial morphology

Lurette, Olivier; Guedouari, Hala; Morris, James B.; Martín-Jiménez, Rebeca; Robichaud, Julie-Pier; Hamel-Côté, Geneviève; Khan, Mehtab; Dauphinee, Nicholas; Pichaud, Nicolas; Prudent, Julien; Hébert-Chatelain, Étienne

doi:10.1007/s00018-022-04325-y

Cited by 9 publications

(5 citation statements)

References 46 publications

(85 reference statements)

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“…Additionally, Src and FAK-activated STAT3 can directly interact with mitochondria to stimulate OXPHOS activity. (Visavadiya et al, 2016, Djeungoue-Petga et al, 2019, Guedouari et al, 2021, Guedouari et al, 2020, Lurette et al, 2022). In contrast, our results show that actin polymerization downstream of these signalling events is required to modulate mitochondrial structure in response to ECM cues in mammospheres.…”

Section: Discussionmentioning

confidence: 98%

Extracellular matrix signals promotes actin-dependent mitochondrial elongation and activity

Gatti,

Mukherjee,

Talukdar

et al. 2024

Preprint

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Mitochondria are crucial metabolic organelles that are regulated by both intracellular and extracellular cues. The extracellular matrix (ECM) is a key component of the cellular environment that controls cellular behavior and metabolic activity. Here, we determined how ECM signalling regulates mitochondrial structure and activity. To distinguish mitochondrial regulation from the general survival cues generated by the ECM, we used breast cancer-derived spheres (mammospheres) because of their ability to grow in suspension culture in the absence of ECM. Using this system, we demonstrate that the association of mammospheres with the ECM results in dramatic mitochondrial elongation, along with enhanced mitochondrial respiration and ATP production. This remodeling occurs independently of DRP1 activity, but relies on integrin signaling and actin polymerization. Therefore, our findings demonstrate that ECM-driven actin polymerization plays a crucial role in remodeling mitochondrial networks to promote OXPHOS, which represents a vital step for migrating cells to enhance cellular adhesion and facilitate cell growth.

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Section: Discussionmentioning

confidence: 98%

Extracellular matrix signals promotes actin-dependent mitochondrial elongation and activity

Gatti,

Mukherjee,

Talukdar

et al. 2024

Preprint

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“…Common mitochondrial dysfunction includes increased ROS production, decreased ATP content due to oxidative phosphorylation, decreased mtDNA biosynthesis, abnormal mitochondrial morphological fusion and division imbalance, autophagy damage, etc. [ 23 ]. MtDNA is an independent double stranded DNA, which is more susceptible to ROS attacks due to the lack of DNA repair enzymes [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate alleviates NAFLD by enhancing the PPARα/PGC-1α signaling pathway coupling mitochondrial function

Wang,

Ying

et al. 2024

BMC Pharmacol Toxicol

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Background To comprehend the influences of fenofibrate on hepatic lipid accumulation and mitochondrial function-related signaling pathways in mice with non-alcoholic fatty liver disease (NAFLD) secondary to high-fat diets together with free fatty acids-influenced HepG2 cells model. Materials and methods A random allocation of male 6-week C57BL/6J mice into three groups was done, including controls, model (14 weeks of a high-fat diet), and fenofibrate [similar to the model one with administered 0.04 g/(kg.d) fenofibrate by gavage at 11 weeks for 4 weeks] groups, which contained 10 mice each. This study verified NAFLD pathogenesis via mitochondrial functions in hepatic pathological abnormalities, liver index and weight, body weight, serum biochemical indexes, oxidative stress indicators, mitochondrial function indexes, and related signaling pathways. The effect of fenofibrate intervention was investigated in NAFLD model mice. In vitro, four groups based on HepG2 cells were generated, including controls, the FFA model (1.5 mmol/L FFA incubation for 24 h), LV-PGC-1α intervention (similar to the FFA model one after PPARGC1A lentivirus transfection), and LV control intervention (similar to the FFA model one after negative control lentivirus transfection) groups. The study investigated the mechanism of PGC-1α related to lipid decomposition and mitochondrial biosynthesis by Oil red O staining, colorimetry and western blot. Results In vivo experiments, a high-fat diet achieved remarkable changes regarding liver weight, liver index, serum biochemical indicators, oxidative stress indicators, liver pathological changes, mitochondrial function indicators, and body weight of the NAFLD model mice while fenofibrate improved the objective indicators. In the HepG2 cells model, the lipid accumulation increased significantly within the FFA model group, together with aggravated hepatocytic damage and boosted oxidative stress levels. Moreover, FFA induced excessive mitosis into fragmented in mitochondrial morphology, ATP content in cells decreased, mtDNA replication fold decreased, the expression of lipid decomposition protein PPARα reduced, mitochondrial biosynthesis related protein PGC-1α, NRF-1 and TFAM decreased. PGC-1α overexpression inhibited lipid deposition by improving mitochondrial biosynthesis and lipid decomposition. Conclusion Fenofibrate up-regulated PPARα/PGC-1α signaling pathway, promoted mitochondrial β-oxidation, reduced oxidative stress damage and lipid accumulation of liver. PGC-1α overexpression enhanced mitochondrial biosynthesis and ATP production, and reduced HepG2 intracellular accumulation of lipids and oxidative stress.

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“…Since the NTM stage is separated from the TM stage by only 8 h [ 47 ], the rapid change in mitochondrial density during florescence indicated that mitochondria underwent fission during this interval. Recent studies showed that mitochondrial elongation enhances cell survival, by increasing respiration to support physical activity [ 48 ], and that the transient and rapid morphological adaptations of mitochondria are crucial for many cellular processes, such as the cell cycle, immunity, apoptosis, and mitochondrial quality control [ 49 ]. In addition, a comparative analysis of TM skunk cabbage with NTM potato and cauliflower showed increased mitochondrial and metabolic activity in skunk cabbage [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Insights into Floral Thermogenesis: In Vivo Analyses of Mitochondrial Dynamics in Nelumbo nucifera Flowers

Wang

et al. 2022

IJMS

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Animal-like thermogenic (TM) activities in flowers have been reported in several families of seed plants. While an association of mitochondria with floral thermogenesis has been described, how mitochondrial dynamics are involved in the regulation of floral thermogenesis is unclear. In this study, the morphological and functional dynamics of mitochondria in vivo were assessed in Nelumbo nucifera Gaertn. flowers during floral thermogenesis. The results showed that mitochondrial biogenesis increased considerably in N. nucifera flowers during thermogenesis, accompanied by notable morphological changes in the mitochondria, including long elliptical, rod-shaped, and dumbbell-shaped morphologies, as well as increased mitochondrial reactive oxygen species (ROS) levels in TM cells. An increase in the expression of alternative oxidase (AOX) during the thermogenesis of N. nucifera flowers was also observed. These observations suggested the rapid change in mitochondrial morphology and increased density during thermogenesis implied activation of mitochondrial fission, which combined with elevated levels of mitochondrial ROS trigger a substantial increase in AOX within the respiratory pathway of TM N. nucifera.

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Mitochondrial matrix-localized Src kinase regulates mitochondrial morphology

Cited by 9 publications

References 46 publications

Extracellular matrix signals promotes actin-dependent mitochondrial elongation and activity

Extracellular matrix signals promotes actin-dependent mitochondrial elongation and activity

Fenofibrate alleviates NAFLD by enhancing the PPARα/PGC-1α signaling pathway coupling mitochondrial function

Novel Insights into Floral Thermogenesis: In Vivo Analyses of Mitochondrial Dynamics in Nelumbo nucifera Flowers

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