About

Vishal Gohil is a professor in the Department of Biochemistry and Biophysics with a focus on mitochondria, mitochondrial respiratory chain, metals, membranes, metabolism, and mitochondrial disorders. His laboratory investigates the biochemical and genetic basis of mitochondrial dysfunctions in rare genetic disorders, aiming to improve molecular diagnosis and develop treatments for these often fatal pediatric conditions. Gohil applies genetics, genomics, and biochemistry techniques using yeast, zebrafish, and mouse models to discover and characterize novel mitochondrial disease-causing genes and to perform targeted drug screens for therapeutic development. His research includes elucidating the role of copper in mitochondrial respiratory chain biogenesis and organismal development, with a particular emphasis on disorders of copper metabolism such as Menkes disease. Gohil's team has identified promising drug candidates like elesclomol, a copper ionophore, which is currently being tested in clinical settings. Additionally, his work explores the requirements of phospholipids like cardiolipin and phosphatidylethanolamine in mitochondrial function, contributing to understanding the pathology of mitochondrial disorders such as Barth syndrome. His research integrates molecular, cellular, and biochemical approaches to uncover the mechanisms underlying mitochondrial diseases and to identify potential therapeutic strategies.

Research topics

• Biochemistry
• Chemistry
• Cell biology
• Biology
• Internal medicine
• Medicine
• Cancer research
• Pathology
• Endocrinology
• Genetics

Selected publications

• A broad-spectrum inhibitor of copper-exporting P _1B -type ATPases

  Proceedings of the National Academy of Sciences · 2026-05-14

  articleOpen access

  Copper (Cu) transporting ATPases represent a highly conserved subclass of P-type ATPases with critical roles in Cu export and metalloenzyme synthesis. Despite their important biological roles and association with a wide range of human diseases, no high-affinity small-molecule inhibitors have been described. Here, we identify MKV3 as a small molecule inhibitor of Cu-transporting P-type ATPases that targets a conserved Cu + entry site to the translocation pathway. In silico docking against the Xenopus ATP7B structure revealed a highly conserved pocket suitable for pharmacological inhibition. MKV3 bound human ATP7A and ATP7B with nanomolar affinity, competed with N-terminal metal-binding domains for access to the Cu + entry site, and selectively inhibited Escherichia coli CopA ATPase activity and Cu + transport. Mechanistically, MKV3 blocked chaperone-mediated Cu + delivery to the intramembranous CPC site of CopA that is essential for its transport function. We further identified a single charged P-domain residue that governed MKV3 affinity and potency across species. Functionally, MKV3 phenocopied the genetic loss of Cu + -ATPases in bacteria, fungi, plants, zebrafish, and mammals, impairing copper-dependent enzymes, transporter trafficking, and copper tolerance. These findings establish a conserved, druggable vulnerability in Cu + -ATPases and introduce MKV3 as a broadly active chemical tool to modulate copper homeostasis across biological kingdoms.

  PublisherOA PDFDOI

• A First-In-Class Broad Spectrum Inhibitor of Copper Exporting P _1B -type ATPases

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-24

  articleOpen access

  Abstract Copper (Cu) transporting ATPases represent a highly conserved subclass of P-type ATPases with critical roles in Cu export and metalloenzyme synthesis. Despite their important biological roles and association with a wide range of human diseases, no high-affinity small-molecule inhibitors have been described. Here, we identify MKV3 as a first-in-class inhibitor of Cu-transporting P-type ATPases that targets a conserved Cu + entry site to the translocation pathway. In silico docking against the Xenopus ATP7B structure revealed a highly conserved pocket suitable for pharmacological inhibition. MKV3 bound human ATP7A and ATP7B with nanomolar affinity, competed with N-terminal metal-binding domains for access to the Cu + entry site, and selectively inhibited Escherichia coli CopA ATPase activity and Cu + transport. Mechanistically, MKV3 blocked chaperone-mediated Cu + delivery to the intramembranous CPC site of CopA that is essential for its transport function. We further identified a single charged P-domain residue that governed MKV3 affinity and potency across species. Functionally, MKV3 phenocopied the genetic loss of Cu + -ATPases in bacteria, fungi, plants, zebrafish, and mammals, impairing copper-dependent enzymes, transporter trafficking, and copper tolerance. These findings establish a conserved, druggable vulnerability in Cu + -ATPases and introduce MKV3 as a broadly active chemical tool to modulate copper homeostasis across biological kingdoms. Significance Statement Copper-transporting P 1B -type ATPases are essential for copper homeostasis in all domains of life, yet have lacked pharmacological inhibitors. This work identifies MKV3 as the first small-molecule inhibitor of Cu + -ATPases in bacteria, fungi, plants and animals, and defines a conserved, druggable Cu + entry pocket that governs metal delivery to the transmembrane pathway. MKV3’s ability to potentiate copper-mediated killing in multidrug-resistant bacterial pathogens highlights its potential as an antimicrobial adjuvant, while its attenuation of mammalian ATP7A/B function offers promise in oncology and copper-related diseases. Collectively, these findings establish a new tool for targeting of Cu + -ATPases with wide-ranging applications across biological systems.

  PublisherOA PDFDOI

• 84 A Rare Case of Crohn's Disease Managed With Vedolizumab and Concurrent Histoplasmosis

  The American Journal of Gastroenterology · 2025-12-01

  article
  PublisherDOI

• Elesclomol-copper therapy improves neurodevelopment in two children with Menkes disease

  Journal of Clinical Investigation · 2025-07-29 · 4 citations

  articleOpen access
  PublisherOA PDFDOI

• Abstract 1102 Repurposing elesclomol for genetic disorders of copper deficiency

  Journal of Biological Chemistry · 2025-05-01

  articleOpen access1st authorCorresponding

  Copper is an essential micronutrient that acts as a catalytic cofactor for enzymes involved in vital cellular functions, including mitochondrial energy generation.Copper deficiency due to genetic defects in copper transporters results in fatal pediatric disorders such as Menkes disease, for which no approved treatment is available.To discover an effective therapeutic agent for these lethal diseases, we designed a targeted yeast-based screen for discovering copper-transporting drugs.Through this screen, we identified elesclomol, an investigational chemotherapy drug, as a potent copper ionophore that transports copper to mitochondria and restores cytochrome c oxidase, an essential cuproenzyme, in yeast, zebrafish, and mice with genetic defects in copper acquisition.Elesclomol improved survival and prevented detrimental neurodegenerative changes in a murine model of severe Menkes disease.Inspired by our studies, the Spanish Agency of Medicines and Health Products recently approved the use of elesclomol-copper in infants with Menkes disease, where the initial results are promising.Our work illustrates how simple model organisms such as yeast can be used to discover human therapeutics for rare genetic disorders.

  PublisherOA PDFDOI

• Nanomaterial-induced mitochondrial biogenesis enhances intercellular mitochondrial transfer efficiency

  Proceedings of the National Academy of Sciences · 2025-10-24 · 7 citations

  articleOpen access

  Intercellular mitochondrial transfer, the spontaneous exchange of mitochondria between cells, is a recently described phenomenon crucial for cellular repair, regeneration, and disease management. Enhancing this natural process holds promise for developing novel therapies targeting diseases associated with mitochondrial dysfunction. Here, we introduce a nanomaterial-based approach employing molybdenum disulfide (MoS 2 ) nanoflowers with atomic-scale vacancies to stimulate mitochondrial biogenesis in cells to make them mitochondrial biofactories. Upon cellular uptake, these nanoflowers result in a two-fold increase in mitochondrial mass and enhancing mitochondrial transfer to recipient cells by several-fold. This enhanced efficiency of transfer significantly improves mitochondrial respiratory capacity and adenosine triphosphate production in recipient cells under physiological conditions. In cellular models of mitochondrial and cellular damage, MoS 2 enhanced mitochondrial transfer achieved remarkable restoration of cell function. This proof-of-concept study demonstrates that nanomaterial-boosted intercellular mitochondrial transfer can enhance cell survivability and function under diseased conditions, offering a promising strategy for treating mitochondrial dysfunction-related diseases.

  PublisherOA PDFDOI

• Mitochondrial dysfunction and lipid dysregulation in yeast lacking phosphatidylserine

  Molecular Biology of the Cell · 2025-08-13 · 1 citations

  articleOpen accessSenior author

  Mitochondrial membrane phospholipids impact mitochondrial structure and function by influencing the assembly and activity of membrane proteins. Although the specific roles of the three most abundant mitochondrial phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL), have been extensively studied, the precise function of less abundant phosphatidylserine (PS) is not yet determined. Here, we used genetic and nutritional manipulation to engineer a set of yeast mutants, including a mutant completely devoid of PS, to assess its role in mitochondrial bioenergetics and lipid homeostasis. To circumvent the confounding effect of downstream PS products, PE and PC, we exogenously supplied ethanolamine that allows their biosynthesis via an alternate pathway. Using this system, we demonstrate that PS does not impact the abundance or the assembly of mitochondrial respiratory chain complexes; however, mitochondrial respiration is impaired. PS-lacking mitochondria cannot maintain mitochondrial membrane potential and exhibit leaky membranes. A mass spectrometry-based analysis of the cellular and mitochondrial lipidomes revealed an unexpected increase in odd-chain fatty acid-containing lipids in PS-lacking cells that may impact mitochondrial bioenergetics. Our study uncovers novel roles of PS in mitochondrial membrane biogenesis and bioenergetics and provides a viable eukaryotic system to unravel the cellular functions of PS.

  PublisherOA PDFDOI

• Atomic vacancies of molybdenum disulfide nanoparticles stimulate mitochondrial biogenesis

  Nature Communications · 2024-09-17 · 19 citations

  articleOpen access

  Diminished mitochondrial function underlies many rare inborn errors of energy metabolism and contributes to more common age-associated metabolic and neurodegenerative disorders. Thus, boosting mitochondrial biogenesis has been proposed as a potential therapeutic approach for these diseases; however, currently we have a limited arsenal of compounds that can stimulate mitochondrial function. In this study, we designed molybdenum disulfide (MoS2) nanoflowers with predefined atomic vacancies that are fabricated by self-assembly of individual two-dimensional MoS2 nanosheets. Treatment of mammalian cells with MoS2 nanoflowers increased mitochondrial biogenesis by induction of PGC-1α and TFAM, which resulted in increased mitochondrial DNA copy number, enhanced expression of nuclear and mitochondrial-DNA encoded genes, and increased levels of mitochondrial respiratory chain proteins. Consistent with increased mitochondrial biogenesis, treatment with MoS2 nanoflowers enhanced mitochondrial respiratory capacity and adenosine triphosphate production in multiple mammalian cell types. Taken together, this study reveals that predefined atomic vacancies in MoS2 nanoflowers stimulate mitochondrial function by upregulating the expression of genes required for mitochondrial biogenesis. Mitochondrial dysfunction is linked to various rare genetic disorders and common age-related diseases, but few compounds can stimulate mitochondrial activity. Here, the authors address this issue by developing atomic vacancy-rich molybdenum disulfide nanoparticles that can catalyze intracellular reactive oxygen species to enhance mitochondrial biogenesis and cellular respiration.

  PublisherOA PDFDOI

• Mechanism of Action and Translational Potential of ( <i>S</i> )-Meclizine in Preemptive Prophylaxis Against Stroke

  Stroke · 2024-04-04 · 2 citations

  articleOpen access

  BACKGROUND: Mild chemical inhibition of mitochondrial respiration can confer resilience against a subsequent stroke or myocardial infarction, also known as preconditioning. However, the lack of chemicals that can safely inhibit mitochondrial respiration has impeded the clinical translation of the preconditioning concept. We previously showed that meclizine, an over-the-counter antivertigo drug, can toggle metabolism from mitochondrial respiration toward glycolysis and protect against ischemia-reperfusion injury in the brain, heart, and kidney. Here, we examine the mechanism of action of meclizine and report the efficacy and improved safety of the (S ) enantiomer. METHODS: We determined the anoxic depolarization latency, tissue and neurological outcomes, and glucose uptake using micro–positron emission tomography after transient middle cerebral artery occlusion in mice pretreated (−17 and −3 hours) with either vehicle or meclizine. To exclude a direct effect on tissue excitability, we also examined spreading depression susceptibility. Furthermore, we accomplished the chiral synthesis of (R )- and (S )-meclizine and compared their effects on oxygen consumption and histamine H1 receptor binding along with their brain concentrations. RESULTS: Micro–positron emission tomography showed meclizine increases glucose uptake in the ischemic penumbra, providing the first in vivo evidence that the neuroprotective effect of meclizine indeed stems from its ability to toggle metabolism toward glycolysis. Consistent with reduced reliance on oxidative phosphorylation to sustain the metabolism, meclizine delayed anoxic depolarization onset after middle cerebral artery occlusion. Moreover, the (S ) enantiomer showed reduced H1 receptor binding, a dose-limiting side effect for the racemate, but retained its effect on mitochondrial respiration. (S )-meclizine was at least as efficacious as the racemate in delaying anoxic depolarization onset and decreasing infarct volumes after middle cerebral artery occlusion. CONCLUSIONS: Our data identify (S )-meclizine as a promising new drug candidate with high translational potential as a chemical preconditioning agent for preemptive prophylaxis in patients with high imminent stroke or myocardial infarction risk.

  PublisherOA PDFDOI

• Elesclomol rescues mitochondrial copper deficiency in disease models without triggering cuproptosis

  Journal of Pharmacology and Experimental Therapeutics · 2024-11-30 · 6 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• Molecular Mechanisms of Copper Delivery to Mitochondrial Cytochrome c Oxidase

  NIH · $2.8M · 2014–2024

Frequent coauthors

• Vamsi K. Mootha

  Broad Institute

  152 shared

• Roland Nilsson

  Karolinska Institutet

  92 shared

• Casey A. Belcher-Timme

  Massachusetts General Hospital

  61 shared

• Sunil A. Sheth

  29 shared

• Daniel H. Arlow

  26 shared

• Zareen Gauhar

  26 shared

• Joshua M. Baughman

  Bristol-Myers Squibb (United States)

  26 shared

• Mohit Jain

  University of California, San Diego

  22 shared

Labs

• Gohil LabPI

Education

• PhD, Department of Biological Sciences

  Wayne State University

  2005