Galectin-8 drives ERK-dependent mitochondrial fragmentation, perinuclear relocation and mitophagy, with metabolic adaptations for cell proliferation DOI Creative Commons
Adely de la Peña, Cláudio Retamal,

Francisca Pérez-Molina

и другие.

European Journal of Cell Biology, Год журнала: 2025, Номер unknown, С. 151488 - 151488

Опубликована: Апрель 1, 2025

Mitochondria adapt to the cell proliferative demands induced by growth factors through dynamic changes in morphology, distribution, and metabolic activity. Galectin-8 (Gal-8), a carbohydrate-binding protein that promotes proliferation transactivating EGFR-ERK signaling pathway, is overexpressed several cancers. However, its impact on mitochondrial dynamics during remains unknown. Using MDCK RPTEC kidney epithelial cells, we demonstrate Gal-8 induces fragmentation perinuclear redistribution. Additionally, mitochondria adopt donut-shaped morphologies, live-cell imaging with two Keima-based reporters demonstrates Gal-8-induced mitophagy. ERK inhibition abrogates all these proliferation. Studies established mutant versions of CHO cells reveal response require interactions between N-terminal carbohydrate recognition domain α-2,3-sialylated N-glycans at surface. DRP1, key regulator fission, becomes phosphorylated or an ERK-dependent manner, mediating Bafilomycin A proliferation, suggesting mitophagy serves as adaptation demands. Functional analysis under stimulation shows maintain active electron transport chain, partially uncoupled from ATP synthesis, increased membrane potential, indicative healthy mitochondria. Meanwhile, exhibit extracellular acidification rate lactate production via aerobic glycolysis, hallmark state. Our findings integrate adaptations potential implications for physiology, disease, therapeutic strategies.

Язык: Английский

Galectin-8 drives ERK-dependent mitochondrial fragmentation, perinuclear relocation and mitophagy, with metabolic adaptations for cell proliferation DOI Creative Commons
Adely de la Peña, Cláudio Retamal,

Francisca Pérez-Molina

и другие.

European Journal of Cell Biology, Год журнала: 2025, Номер unknown, С. 151488 - 151488

Опубликована: Апрель 1, 2025

Mitochondria adapt to the cell proliferative demands induced by growth factors through dynamic changes in morphology, distribution, and metabolic activity. Galectin-8 (Gal-8), a carbohydrate-binding protein that promotes proliferation transactivating EGFR-ERK signaling pathway, is overexpressed several cancers. However, its impact on mitochondrial dynamics during remains unknown. Using MDCK RPTEC kidney epithelial cells, we demonstrate Gal-8 induces fragmentation perinuclear redistribution. Additionally, mitochondria adopt donut-shaped morphologies, live-cell imaging with two Keima-based reporters demonstrates Gal-8-induced mitophagy. ERK inhibition abrogates all these proliferation. Studies established mutant versions of CHO cells reveal response require interactions between N-terminal carbohydrate recognition domain α-2,3-sialylated N-glycans at surface. DRP1, key regulator fission, becomes phosphorylated or an ERK-dependent manner, mediating Bafilomycin A proliferation, suggesting mitophagy serves as adaptation demands. Functional analysis under stimulation shows maintain active electron transport chain, partially uncoupled from ATP synthesis, increased membrane potential, indicative healthy mitochondria. Meanwhile, exhibit extracellular acidification rate lactate production via aerobic glycolysis, hallmark state. Our findings integrate adaptations potential implications for physiology, disease, therapeutic strategies.

Язык: Английский

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