Explanipedia

A noncanonical cGAS–STING pathway drives cellular and organismal aging Open

Rafael Cançado de Faria, Lílian Nara David e Silva, Barbara Teodoro-Castro, Kyle S. McCommis, Elena V. Shashkova , et al. · 2025

Accumulation of cytosolic DNA has emerged as a hallmark of aging, inducing sterile inflammation. Stimulator of interferon genes (STING) protein translates the sensing of cytosolic DNA by cyclic-GMP-AMP synthase (cGAS) into an inflammatory …

At last: the mitochondrial pyruvate carrier structure revealed! Open

Brian N. Finck, C. Hadfield, Kyle S. McCommis · 2025

Mitochondrial pyruvate carrier (MPC) inhibitors have shown promise as therapeutics for treating several chronic diseases. However, the structure of MPC and the molecular mechanisms by which it interacts with inhibitors have remained unclea…

A non-canonical cGAS-STING pathway drives cellular and organismal aging Open

Rafael Cançado de Faria, Lilian de Souza D’Albuquerque Silva, Barbara Teodoro-Castro, Kyle S. McCommis, Elena V. Shashkova , et al. · 2025

Accumulation of cytosolic DNA has emerged as a hallmark of aging, inducing sterile inflammation. STING (Stimulator of Interferon Genes) protein translates the sensing of cytosolic DNA by cGAS (cyclic-GMP-AMP synthase) into an inflammatory …

Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways Open

Debojyoty Bandyopadhyay, Ellen T. Tran, Rajan Patel, Matthew Luetzen, Kevin Cho , et al. · 2024

One of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon)…

Advancing mitochondrial therapeutics: Synthesis and pharmacological evaluation of pyrazole-based inhibitors targeting the mitochondrial pyruvate carrier Open

Lingaiah Maram, Jessica M. Michael, Henry Politte, Vaishnavi S. Srirama, A Hadji , et al. · 2024

Inhibition of mitochondrial pyruvate transport via the mitochondrial pyruvate carrier (MPC) has shown beneficial effects in treating metabolic diseases, certain cancers, various forms of neurodegeneration, and hair loss. These benefits ari…

2-Chloro- and 2-Bromopalmitic acids inhibit mitochondrial function in airway epithelial cells Open

Karina Ricart, Kyle S. McCommis, David A. Ford, Rakesh P. Patel · 2024

2-Chloropalmitic acid (2-ClPA) and 2-bromopalmitic acid (2-BrPa) increase in inflammatory lung disease associated with formation of hypochlorous or hypobromous acid, and exposure to halogen gases. Moreover, these lipids may elicit cell res…

Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer Open

Ronald Fowle-Grider, Joe L. Rowles, Isabel Shen, Yahui Wang, Michaela Schwaiger-Haber , et al. · 2024

Membrane lipid nanodomains modulate HCN pacemaker channels in nociceptor DRG neurons Open

Lucas J. Handlin, Natalie L. Macchi, Nicolas Dumaire, Lyuba Salih, Erin N. Lessie , et al. · 2024

Cell membranes consist of heterogeneous lipid nanodomains that influence key cellular processes. Using FRET-based fluorescent assays and fluorescence lifetime imaging microscopy (FLIM), we find that the dimension of cholesterol-enriched or…

Ketone Body Metabolism is Not Required for Improvement of Heart Failure by Ketogenic Diet in Mice Open

Zachary Foulks, Carla J. Weinheimer, Attila Kovács, Jessica Michael, Kelly D. Pyles , et al. · 2024

Failing hearts increasingly metabolize ketone bodies, and enhancing ketosis improves heart failure (HF) remodeling. Circulating ketones are elevated by fasting/starvation, which is mimicked with a high-fat, low-carbohydrate “ketogenic diet…

Etomoxir: an old dog with new tricks Open

Reagan M McGuffee, Kyle S. McCommis, David A. Ford · 2024

Loss of mitochondrial pyruvate transport initiates cardiac glycogen accumulation and heart failure Open

Rachel C. Weiss, Kelly D. Pyles, Kevin Cho, Michelle Brennan, Jonathan S. Fisher , et al. · 2024

Heart failure involves metabolic alterations including increased glycolysis despite unchanged or decreased glucose oxidation. The mitochondrial pyruvate carrier (MPC) regulates pyruvate entry into the mitochondrial matrix, and cardiac dele…

Computational structural prediction and chemical inhibition of the human mitochondrial pyruvate carrier protein heterodimer complex Open

C. Hadfield, John K. Walker, Reza Dastvan, Chris Arnatt, Kyle S. McCommis · 2024

The mitochondrial pyruvate carrier (MPC) plays a role in numerous diseases including neurodegeneration, metabolically dependent cancers, and the development of insulin resistance. Several previous studies in genetic mouse models or with ex…

Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk Open

Alexander Piening, E C Ebert, Carter Gottlieb, Niloufar Khojandi, Lindsey M. Kuehm , et al. · 2024

In chronic kidney disease altered cardiac metabolism precedes cardiac hypertrophy Open

Matthew J. Williams, Carmen M. Halabi, Hiral Patel, Zachary Joseph, Kyle S. McCommis , et al. · 2024

Heart disease is an important morbidity of chronic kidney disease (CKD). Hypertension, vascular stiffness, and vascular calcification all contribute to cardiac pathophysiology. However, cardiac function in CKD devoid of vascular disease ha…

Advancing Mitochondrial Therapeutics: Synthesis and Pharmacological Evaluation of Pyrazole-Based Inhibitors Targeting the Mitochondrial Pyruvate Carrier Open

Lingaiah Maram, Jessica M. Michael, Henry Politte, Vaishnavi S. Srirama, A Hadji , et al. · 2024

Metabolic Drivers and Rescuers of Heart Failure. Open

Rachel C. Weiss, Thiago N. Menezes, Kyle S. McCommis · 2023

Cardiac hypertrophy and heart failure involve a number of metabolic alterations. Human genetic mutations and murine genetic deficiency models of metabolic enzymes or transporters largely suggest that these alterations in metabolism are mal…

Hepatic pyruvate and alanine metabolism are critical and complementary for maintenance of antioxidant capacity and resistance to oxidative insult Open

Nicole K.H. Yiew, Joel H. Vazquez, Michael R. Martino, Stefanie Kennon‐McGill, Jake R. Price , et al. · 2023

Membrane Lipid Nanodomains Modulate HCN Pacemaker Channels in Nociceptor DRG Neurons Open

Lucas J. Handlin, Natalie L. Macchi, Nicolas Dumaire, Lyuba Salih, Erin N. Lessie , et al. · 2023

Cell membranes consist of heterogeneous lipid nanodomains that influence key cellular processes. Using FRET-based fluorescent assays and fluorescence lifetime imaging microscopy (FLIM), we found that the dimension of cholesterol-enriched o…

Editorial: Diabetes and non-alcoholic fatty liver disease: points of physiological and mechanistic intersection and current co-therapeutic approaches Open

Nick Giannoukakis, Kyle S. McCommis · 2023

EDITORIAL article Front. Endocrinol., 17 July 2023Sec. Diabetes: Molecular Mechanisms Volume 14 - 2023 | https://doi.org/10.3389/fendo.2023.1253604

Ube4A maintains metabolic homeostasis and facilitates insulin signaling in vivo Open

Sandip Mukherjee, Molee Chakraborty, Eliwaza Naomi Msengi, Jake Haubner, Jinsong Zhang , et al. · 2023

STAT1 Drives the Interferon-Like Response and Aging Hallmarks in Progeria Open

Susana Gonzalo, Rafael Cançado de Faria, Elena V. Shashkova, Colin A. Flaveny, Ángel Baldán , et al. · 2023

Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disease caused by the mutant lamin-A protein "progerin," features robust sterile inflammation/interferon (IFN)-like response. Targeting inflammation delays cellular…

Data from Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy Open

Lindsey M. Kuehm, Niloufar Khojandi, Alexander Piening, Lauryn E. Klevorn, Simone C. Geraud , et al. · 2023

Checkpoint blockade immunotherapy relies on the empowerment of the immune system to fight cancer. Why some patients fail to achieve durable clinical responses is not well understood, but unique individual factors such as diet, obesity, and…

Data from Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy Open

Lindsey M. Kuehm, Niloufar Khojandi, Alexander Piening, Lauryn E. Klevorn, Simone C. Geraud , et al. · 2023

Checkpoint blockade immunotherapy relies on the empowerment of the immune system to fight cancer. Why some patients fail to achieve durable clinical responses is not well understood, but unique individual factors such as diet, obesity, and…

Supplemental Figures S1-S9 from Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy Open

Lindsey M. Kuehm, Niloufar Khojandi, Alexander Piening, Lauryn E. Klevorn, Simone C. Geraud , et al. · 2023

Supplemental Figs S1-S9

Supplemental Figures S1-S9 from Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy Open

Lindsey M. Kuehm, Niloufar Khojandi, Alexander Piening, Lauryn E. Klevorn, Simone C. Geraud , et al. · 2023

Supplemental Figs S1-S9

Mitochondrial pyruvate carrier inhibition initiates metabolic crosstalk to stimulate branched chain amino acid catabolism Open

Daniel Ferguson, Sophie J. Eichler, Nicole K.H. Yiew, Jerry R. Colca, Kevin Cho , et al. · 2023

These data demonstrate novel cross talk between mitochondrial pyruvate and BCAA metabolism and suggest that MPC inhibition leads to lower plasma BCAA concentrations and BCKDH phosphorylation by activating the mTOR axis. However, the effect…

The Hepatic Mitochondrial Pyruvate Carrier as a Regulator of Systemic Metabolism and a Therapeutic Target for Treating Metabolic Disease Open

Kyle S. McCommis, Brian N. Finck · 2023

Pyruvate sits at an important metabolic crossroads of intermediary metabolism. As a product of glycolysis in the cytosol, it must be transported into the mitochondrial matrix for the energy stored in this nutrient to be fully harnessed to …

A dual MTOR/NAD+ acting gerotherapy Open

Jinmei Li, Sandeep Kumar, Kirill Miachin, Nicholas L. Bean, Ornella Halawi , et al. · 2023

The geroscience hypothesis states that a therapy that prevents the underlying aging process should prevent multiple aging related diseases. The mTOR (mechanistic target of rapamycin)/insulin and NAD+ (nicotinamide adenine dinucleotide) pat…

Enhancing Hepatic MBOAT7 Expression in Mice With Nonalcoholic Steatohepatitis Open

Martin C. Sharpe, Kelly D. Pyles, Taylor Hallcox, Dakota R. Kamm, Michaela Piechowski , et al. · 2023

Results suggest decreased MBOAT7 activity plays a role in NASH, but MBOAT7 overexpression fails to measurably improve NASH pathology potentially due to the insufficient abundance of its arachidonoyl-CoA substrate.

Myeloperoxidase-derived hypochlorous acid targets human airway epithelial plasmalogens liberating protein modifying electrophilic 2-chlorofatty aldehydes Open

Shubha Shakya, Kelly D. Pyles, Carolyn J. Albert, Rakesh P. Patel, Kyle S. McCommis , et al. · 2022

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