Biology subjects

Kaushik, G.

Publications and source records attributed to Kaushik, G..

3 recordsLinked to original sources

bioRxiv2026

VDAC1 regulates stress-associated matrix localization of DJ-1 to support mitochondrial homeostasis and neuronal survival

DJ-1 is a redox-sensitive protein implicated in early-onset Parkinson's disease, and its mitochondrial localization protects against oxidative stress, but the mechanisms regulating its submitochondrial targeting and functional impact on mitochondrial integrity remain poorly understood. We identify voltage-dependent anion channel 1 (VDAC1) as a regulator of the submitochondrial distribution of DJ-1 during stress. Endogenous DJ-1 interacted with VDAC1, and loss of VDAC1 reduced stress-induced DJ-1 accumulation within the mitochondrial matrix. VDAC1-deficient neurons exhibited mitochondrial fragmentation, impaired oxidative phosphorylation, reduced ATP levels, altered reactive oxygen species (ROS) responses, and increased sensitivity to MPP+;. Matrix-targeted, but not outer-membrane-targeted, DJ-1 rescued basal, ATP-linked, and maximal respiration, improved mitochondrial morphology, and enhanced neuronal survival. ATP synthase inhibition also rapidly increased mitochondrial DJ-1, suggesting bioenergetic stress promotes its mitochondrial accumulation. Our findings identify compartment-specific localization as a key determinant of DJ-1 function and establish VDAC1-dependent matrix targeting as a critical mechanism supporting mitochondrial integrity during stress.

neuroscience↗

bioRxiv2025

Individual dopaminergic neurons induce unique, yet overlapping combinations of behavioural modulations including safety learning, memory retrieval and acute locomotion

Two evolutionary highly conserved functions of dopamine are to carry "teaching" signals during associative learning and to control movement. In mammals and humans, these functions are generally thought to be produced by different populations of neurons. Here, we investigated in the larva of Drosophila melanogaster whether both these functions can be induced by the same individual dopaminergic neurons in the central brain. Focusing on the dopaminergic neurons of the DL1-cluster, we asked whether the optogenetic activation of individual neurons established associative punishment and/or safety memories, controlled the retrieval of the established memories, and acutely modulated locomotion. We found that each neuron had a unique, yet overlapping set of behavioural effects. Several individual neurons both established a memory and modulated acute locomotion by increasing the animals bending and decreasing its velocity. Our results demonstrate that individual dopaminergic neurons can fulfil a surprisingly broad range of functions in different behavioural contexts. Given the highly conserved roles of the dopaminergic system across the animal kingdom, this study raises the question whether a similarly diverse functionality can be found also in other animals, including humans.

neuroscience↗

bioRxiv2022

EXPOSURE TO GLYPHOSATE OR ROUNDUP DURING ZEBRAFISH EMBRYOGENESIS DIFFERENTIALLY AFFECTS METABOLISM AND SWIMMING BEHAVIOURS

Glyphosate-based herbicides (GBHs), the most recognized of which is Roundup, are the most extensively used herbicides worldwide. GBHs were initially considered safe for animals since the primary target of the active ingredient, glyphosate, is only found in plants. Recent studies show that glyphosate can affect a range of animal physiologies; however, it remains poorly characterized as to whether animal GBH effects are mediated by glyphosate itself or are in response to toxic effects of the adjuvants and surfactants found in GBH formulations. Here we expose embryonic zebrafish to environmentally relevant doses of glyphosate or Roundup and compare effects on two systems in the larvae: cellular bioenergetics, since glyphosate can affect mitochondrial function, and behaviour, as a systems-level readout of lasting developmental changes. We showed that exposure of embryonic zebrafish to low levels of glyphosate resulted in decreased mitochondrially-mediated basal respiration and hypoactive swimming behavior in larval stage, whereas exposure to Roundup in this same treatment paradigm had the opposite effect, causing increased cellular respiration and increased locomotion. In addition, we also explored generational effects of F1 embryonic glyphosate or Roundup exposure in the F2, and showed that offspring born to zebrafish exposed to low-level glyphosate or Roundup during embryogenesis both exhibited reduced mitochondrially-mediated basal respiration and altered locomotion. Combined, these data show that embryonic exposure to glyphosate or the full formulation of GBHs caused differential effects on mitochondrial function and behaviours in vertebrates, with potential lasting effects on future generations. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/510731v1_fig1.gif" ALT="Figure 1"> View larger version (12K): org.highwire.dtl.DTLVardef@93431borg.highwire.dtl.DTLVardef@1aa602org.highwire.dtl.DTLVardef@1890cf5org.highwire.dtl.DTLVardef@b1c655_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Graphical abstract.Zebrafish (F1 generation) were exposed to glyphosate or Roundup from zero to 48 hours, with behaviour and mitochondrial bioenergetics assessed at larval timepoints (2- and 5-dpf). Offspring of glyphosate and Roundup exposed fish (F2 generation) behaviour and mitochondrial bioenergetics were assessed to the same paradigm as F1 fish at 5-dpf. Changes to core metabolic parameters and locomotion was observed in both F1 and F2 generations. C_FIG

neuroscience↗