Explanipedia

Influenza A infection accelerates disease-associated microglia formation during physiological aging Open

Rogan A. Grant, Constance E. Runyan, Grace Minogue, Joshua S. Stoolman, Satoshi Watanabe , et al. · 2025

Severe pneumonia is associated with an increased risk of cognitive decline and dementia, particularly in the elderly. Changes in microglia, the most abundant immune cell population in the brain, are also associated with cognitive decline a…

Intrinsic MicroRNA‐10a Restricts Regulatory T Cell Suppressive Function and Intestinal Repair by Coordinating Transcriptional, Metabolic, and Epithelial Repair Pathways Open

Wenjing Yang, Tianming Yu, Hui Yang, Suxia Yao, Ronald C.W. , et al. · 2025

Regulatory T cells (Tregs) are indispensable for maintaining immune homeostasis and suppressing excessive inflammatory responses in the intestine. While much attention has focused on positive regulators of Treg differentiation and function…

NADH dehydrogenase reverses dietary and clock metabolic syndrome Open

Chelsea Hepler, Nathan J. Waldeck, Benjamin J. Weidemann, Biliana Marcheva, Hsuan‐An Su , et al. · 2025

Circadian clocks are internal timing systems that enable organisms to anticipate and adapt to daily environmental changes. These rhythms arise from a transcription-translation feedback loop in which CLOCK/BMAL1 regulate the expression of t…

Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycemic control Open

Zachary L. Sebo, Ram Prosad Chakrabarty, Rogan A. Grant, Karis B. D’Alessandro, Alec Koss , et al. · 2025

Metformin is a therapeutically versatile biguanide drug primarily prescribed for type II diabetes. Despite its extensive use, the mechanisms underlying many of its clinical effects, including attenuated postprandial glucose excursions, ele…

SGLT2 inhibition protects kidney function by SAM-dependent epigenetic repression of inflammatory genes under metabolic stress Open

Hiroshi Maekawa, Yalu Zhou, Yuki Aoi, Margaret E. Fain, Dorian Kaminski , et al. · 2025

Clinically, blockade of renal glucose resorption by sodium-glucose cotransporter 2 (SGLT2) inhibitors slows progression of kidney disease, yet the underlying mechanisms are not fully understood. We hypothesized that altered renal metabolit…

Genetic modulation of mitochondrial NAD+ regeneration does not prevent dopaminergic neuron dysfunction caused by mitochondrial complex I impairment Open

Karis B. D’Alessandro, Enrico Zampese, Jenna L. E. Blum, Britta Kuusik, Alec Palmiotti , et al. · 2025

Dysfunction of mitochondrial complex I (MCI) has been implicated in the degeneration of dopaminergic neurons in Parkinson’s disease. Here, we report the effect of expressing MitoLbNOX, a mitochondrial-targeted version of the bacterial enzy…

Aspartate transaminases are required for blood development Open

Narges Pourmandi, Greggory Myers, Amit K. Jha, Kelsey Temprine, Amanda Sankar , et al. · 2025

Red blood cells (RBCs) have a limited lifespan of approximately 120 days. This necessitates continuous RBC production, resulting in ∼200 billion new RBCs made per day to maintain oxygen delivery. Despite this enormous biosynthetic demand, …

Mitochondrial activity tunes nociceptor resilience to excitotoxicity Open

Lin Yuan, Navdeep S. Chandel, David Julius · 2025

Large language models accurately identify immunosuppression in intensive care unit patients Open

Vijeeth Guggilla, Mengjia Kang, M. Bak, Steven Tran, Anna Pawlowski , et al. · 2025

Objective Rule-based structured data algorithms and natural language processing (NLP) approaches applied to unstructured clinical notes have limited accuracy and poor generalizability for identifying immunosuppression. Large language model…

Mitochondria reactive oxygen species signaling in immune responses Open

Samuel E. Weinberg, Navdeep S. Chandel · 2025

Mitochondria are key regulators of immune cell function, going beyond their traditional role in ATP and metabolite production to support anabolic processes and act as hubs for intracellular signaling. A key aspect of this signaling functio…

G1 and G2 ApolipoproteinL1 modulate macrophage inflammation and lipid accumulation through the polyamine pathway Open

Esther Liu, Matthew C. Wright, Andrew O Kearney, Tiffany Caza, Johnson Y Yang , et al. · 2025

The G1 and G2 variants of the gene encoding Apolipoprotein L1 (APOL1) increase risk for kidney disease and cardiometabolic traits. While previous studies have elucidated key mechanisms by which G1 and G2 APOL1 cause cellular inflammation a…

G1 and G2 ApolipoproteinL1 modulate macrophage inflammation and lipid accumulation through the polyamine pathway Open

Esther Liu, Matthew C. Wright, Andrew O Kearney, Tiffany Caza, Johnson Y Yang , et al. · 2025

The G1 and G2 variants of the gene encoding Apolipoprotein L1 (APOL1) increase risk for kidney disease and cardiometabolic traits. While previous studies have elucidated key mechanisms by which G1 and G2 APOL1 cause cellular inflammation a…

Mitochondrial respiration is necessary for CD8+ T cell proliferation and cell fate Open

Elizabeth M. Steinert, Beatriz Furtado Bruza, Veronika Denise Danchine, Rogan A. Grant, Karthik Vasan , et al. · 2025

Impaired mitochondrial metabolism is a critical cancer vulnerability for MYC inhibitors Open

William Y. Yang, Qianyu Guo, Songhua Quan, Zachary R. Chalmers, J. Brandon Parker , et al. · 2025

MYC is a key driver in many aggressive and therapy-resistant cancers. We have developed and characterized a small-molecule MYC inhibitor named MYCi975. To uncover combination strategies for MYC inhibitors, we conducted a genome-wide CRISPR…

Mitochondria dysfunction: cause or consequence of physiologic aging? Open

G. R. Scott Budinger, Navdeep S. Chandel · 2025

Mitochondria are no longer viewed solely as ATP- or metabolite-generating organelles but as key regulators of cellular signaling that shape physiologic aging. Contrary to earlier theories linking aging to mitochondrial DNA mutations and ox…

Treg activation during allograft tolerance induction requires mitochondrion-induced TGF-β1 in type 1 conventional dendritic cells Open

Samantha L. Schroth, Lei Zhang, Rebecca Jones, Kristofor Glinton, Nikita Mani , et al. · 2025

The role of conventional type 1 DCs (cDC1s) in tolerance induction to solid organ allografts is unknown and important for strategies that seek to prolong allograft viability. Using a murine model deficient in cDC1s, we report cDC1s are req…

G1 and G2 ApolipoproteinL1 modulate macrophage inflammation and lipid accumulation through the polyamine pathway Open

Esther Liu, Matthew C. Wright, Andrew O Kearney, Tiffany Caza, Johnson Y Yang , et al. · 2025

The G1 and G2 variants of the gene encoding Apolipoprotein L1 ( APOL1 ) increase risk for kidney disease and cardiometabolic traits. While previous studies have elucidated key mechanisms by which G1 and G2 APOL1 cause cellular inflammation…

Genetic modulation of mitochondrial NAD+ regeneration does not prevent dopaminergic neuron dysfunction caused by mitochondrial complex I impairment Open

Karis B. D’Alessandro, Enrico Zampese, Jenna L. E. Blum, Britta Kuusik, Alec Palmiotti , et al. · 2025

Dysfunction of mitochondrial complex I (MCI) has been implicated in the degeneration of dopaminergic neurons in Parkinson’s disease. Here, we report the effect of expressing MitoLbNOX, a mitochondrial-targeted version of the bacterial enzy…

CRISPR screen reveals a simultaneous targeted mechanism to reduce cancer cell selenium and increase lipid oxidation to induce ferroptosis Open

Sophia Lamperis, Kaylin M. McMahon, Andrea E. Calvert, Jonathan S. Rink, Karthik Vasan , et al. · 2025

Ferroptosis is a cell death mechanism distinguished by its dependence on iron-mediated lipid oxidation. Cancer cells highly resistant to conventional therapies often demonstrate lipid metabolic and redox vulnerabilities that sensitize them…

Abstract 1748 Activation of the Integrated Stress Response during hypercapnia prevents alveolar type 2 cells differentiation and induce lung injury Open

Laura A. Dada, Lynn C. Welch, Sofía Reynoso, Lucía Martínez‐Santamaría, Ziyou Ren , et al. · 2025

Abstract 2680 Principles of mitochondria as signaling organelles Open

Navdeep S. Chandel · 2025

Endothelial Prolyl Hydroxylase 3 Mitigates Maladaptive Inflammation to Promote Post-Ischemic Kidney Repair Open

Rajni Sharma, Ratnakar Tiwari, James O’Sullivan, G. Borkowski, Si Young An , et al. · 2025

Acute kidney injury (AKI) is a major health concern and well-established risk factor for the development of chronic kidney disease (CKD). Tissue hypoxia is a prominent feature of the injured kidney that shapes the biological behavior of pa…

Microglial Fructose Metabolism Is Essential for Glioblastoma Growth Open

Leah K. Billingham, Shashwat Tripathi, Ian Olson, Ian Olson, Kaylee Zilinger , et al. · 2025

Glioblastoma (GBM) is most common and aggressive primary brain tumor in adults, for which standard of care hasn’t changed in twenty years. GBM tumor associated macrophages (TAMCs), consisting of infiltrating myeloid cells from the peripher…

A metabolic shift to the serine pathway induced by lipids fosters epigenetic reprogramming in nontransformed breast cells Open

Mariana Bustamante Eduardo, Gannon Cottone, Curtis W. McCloskey, Shiyu Liu, Flávio R. Palma , et al. · 2025

Lipid metabolism and the serine, one-carbon, glycine (SOG) and methionine pathways are independently and significantly correlated with estrogen receptor–negative breast cancer (ERneg BC). Here, we propose a link between lipid metabolism an…

Immunomodulatory role of the stem cell circadian clock in muscle repair Open

Pei Zhu, Eric M. Pfrender, Adam W. T. Steffeck, Colleen R. Reczek, Yalu Zhou , et al. · 2025

Circadian rhythms orchestrate physiological processes such as metabolism, immune function, and tissue regeneration, aligning them with the optimal time of day (TOD). This study identifies an interplay between the circadian clock within mus…

Pathway Coessentiality Mapping Reveals Complex II is Required for <i>de novo</i> Purine Biosynthesis in Acute Myeloid Leukemia Open

Amy E. Stewart, Derek K. Zachman, Pol Castellano‐Escuder, Loïs Kelly, Ben Zolyomi , et al. · 2025

Understanding how cellular pathways interact is crucial for treating complex diseases like cancer, yet our ability to map these connections systematically remains limited. Individual gene-gene interaction studies have provided insights 1,2…

Mitochondria complex III–generated superoxide is essential for IL-10 secretion in macrophages Open

Joshua S. Stoolman, Rogan A. Grant, Leah K. Billingham, Taylor A. Poor, Samuel E. Weinberg , et al. · 2025

Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of macrophage immune responses are not fully understood. Here, we report that mutant mice with mito…

Tissue-resident skeletal muscle macrophages promote recovery from viral pneumonia-induced sarcopenia in normal aging Open

Constance E. Runyan, Lucy Luo, Lynn C. Welch, Ziyan Lu, Fei Chen , et al. · 2025

Sarcopenia, which diminishes lifespan and healthspan in the elderly, is commonly exacerbated by viral pneumonia, including influenza and COVID-19. In a study of influenza A pneumonia in mice, young mice fully recovered from sarcopenia, whi…

Effects of Xylitol on Tumor Progression in Syngeneic Mice Cancer Models Open

Mark Cannon, Ashlee Cosantino, Lori Tran, Navdeep S. Chandel, Nayereh Ghoreishi · 2025

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol is known for its dental health benefits, but emerging evidence suggests broader biological roles, inclu…

Metabolic tuning facilitates nociceptor resilience to excitotoxicity Open

Lin Yuan, Navdeep S. Chandel, David Julius · 2024

The capsaicin receptor, TRPV1, mediates the detection of harmful chemical and thermal stimuli. Overactivation of TRPV1 can lead to cellular damage or death through excitotoxicity, a phenomenon associated with painful neuropathy and the par…

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