Biology subjects

Segura, I.

Publications and source records attributed to Segura, I..

3 recordsLinked to original sources

bioRxiv2026

A Na⁺-PINK1 signaling axis couples mitochondrial fission to structural remodeling during synaptic depression

Mitochondrial density in dendrites adapts to the number of synaptic inputs to adequately sustain local ATP and Ca2+ buffering for neuronal signaling. During long-term depression (LTD), synapse elimination is accompanied by activation of caspase-3 through sublethal mitochondria-derived apoptotic signals, driving neurotransmitter receptor internalization and spine shrinking. However, the upstream signals that link synaptic activity to mitochondrial remodeling remain unknown. Here we show that Na+ influx through NMDA receptors depolarizes mitochondria during chemically induced LTD. This triggers stabilization and activation of the PINK1 kinase in a translation-dependent manner, leading to asynchronous mitochondrial fission. Na+ influx and PINK1 are required for cLTD-induced fission, and blocking either Na+ influx or PINK1 prevents caspase-3 activation and spine shrinking in cultured neurons. Together, these findings identify a Na+-PINK1 signaling axis that couples NMDA receptor activity to mitochondrial fission and caspase-3-dependent synapse elimination during LTD, with implications for the homeostatic regulation of synaptic density.

neuroscience↗

bioRxiv2024

ER-associated biogenesis of PINK1 preprotein for neuronal mitophagy

A central role in mitochondrial quality control is played by the Parkinson-related mitochondrial kinase PINK1, whose mRNA is transported in neurons by mitochondrial hitch- hiking. Using a live-cell imaging assay for the translation of the PINK1 precursor, we show that local translation of PINK1 requires a concerted interplay between mitochondria and the ER in neurons. For efficient translation, the Pink1 mRNA needs to relocate to ribosomes located near endolysosomes and the ER. The ER membrane-tethered chaperone DNAJB6 then shields the PINK1 precursor on transit to mitochondria following the ER-SURF pathway. Loss of DNAJB6 hence leads to persistence of ER/endolysosome-associated PINK1 precursor stores and failure of mitophagy upon mitochondrial damage.

neuroscience↗

bioRxiv2020

Large-scale monitoring of resistance to coumaphos, amitraz and pyrethroids in Varroa destructor

Varroa destructor is an ectoparasitic mite causing devastating damages to honey bee colonies around the world. Its impact is considered a major factor contributing to the significant seasonal losses of colonies recorded every year. Beekeepers are usually relying on a reduced set of acaricides to manage the parasite, usually the pyrethroids tau-fluvalinate or flumethrin, the organophosphate coumaphos and the formamidine amitraz. However, the evolution of resistance in the populations is leading to an unsustainable scenario with almost no alternatives to reach an adequate control of the mite. Here we present the results from the first, large-scale and extensive monitoring of the susceptibility to acaricides in the Comunitat Valenciana, one of the most prominent apicultural regions in Spain. Our ultimate goal was to provide beekeepers with timely information to help them decide what would be the best alternative for a long-term control of the mites in their apiaries. Our data show that there is a significant variation in the expected efficacy of coumaphos and pyrethroids across the region, indicating the presence of a different ratio of resistant individuals to these acaricides in each population. On the other hand, the expected efficacy of amitraz was more consistent, although slightly below the expected efficacy according to the label. HIGHLIGHTSO_LIVarroa destructor is causing severe damages to honey bee colonies worldwide. C_LIO_LIThere are very few acaricides available to manage the parasite. C_LIO_LIThe evolution of resistance is limiting our capacity to control the mite. C_LIO_LIWe estimated the expected efficacy of the main acaricides in many Spanish apiaries. C_LIO_LIThe information was shared with beekeepers for them to decide the best treatment to control the mite. C_LI

pharmacology and toxicology↗