bims-celmim Biomed News
on Cellular and mitochondrial metabolism
Issue of 2024‒09‒01
eighteen papers selected by
Marc Segarra Mondejar
  1. Drp1 depletion protects against ferroptotic cell death by preserving mitochondrial integrity and redox homeostasis.
  2. Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2.
  3. The unique catalytic properties of PSAT1 mediate metabolic adaptation to glutamine blockade.
  4. Amino acid metabolism in kidney health and disease.
  5. Infection-induced peripheral mitochondria fission drives ER encapsulations and inter-mitochondria contacts that rescue bioenergetics.
  6. Metabolic and Oxidative Stress Management Heterogeneity in a Panel of Breast Cancer Cell Lines.
  7. Lactate helps cancer cells resist chemotherapy.
  8. Mitochondrial membrane lipids in the regulation of bioenergetic flux.
  9. Structural basis for allosteric regulation of human phosphofructokinase-1.
  10. An economic demand-based framework for prioritization strategies in response to transient amino acid limitations.
  11. Detailed analysis of Mdivi-1 effects on complex I and respiratory supercomplex assembly.
  12. Mitochondrial serine catabolism safeguards maintenance of the hematopoietic stem cell pool in homeostasis and injury.
  13. Mitochondrial calcium uniporter channel gatekeeping in cardiovascular disease.
  14. Function of CSNK2/CK2 selectively affects the endoplasmic reticulum and the Golgi apparatus in mtor-mediated autophagy induction.
  15. Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.
  16. [Molecular mechanism of CDO1 regulating common metabolic diseases].
  17. The role of mitochondrial fusion and fission in immune-mediated inflammatory diseases.
  18. Exploring the heterogeneous targets of metabolic aging at single-cell resolution.
  1. Cell Death Dis. 2024 Aug 27. 15(8): 626
    Drp1 depletion protects against ferroptotic cell death by preserving mitochondrial integrity and redox homeostasis.
    Stephan Tang, Anneke Fuß, Zohreh Fattahi, Carsten Culmsee.
      Mitochondria are highly dynamic organelles which undergo constant fusion and fission as part of the mitochondrial quality control. In genetic diseases and age-related neurodegenerative disorders, altered mitochondrial fission-fusion dynamics have been linked to impaired mitochondrial quality control, disrupted organelle integrity and function, thereby promoting neural dysfunction and death. The key enzyme regulating mitochondrial fission is the GTPase Dynamin-related Protein 1 (Drp1), which is also considered as a key player in mitochondrial pathways of regulated cell death. In particular, increasing evidence suggests a role for impaired mitochondrial dynamics and integrity in ferroptosis, which is an iron-dependent oxidative cell death pathway with relevance in neurodegeneration. In this study, we demonstrate that CRISPR/Cas9-mediated genetic depletion of Drp1 exerted protective effects against oxidative cell death by ferroptosis through preserved mitochondrial integrity and maintained redox homeostasis. Knockout of Drp1 resulted in mitochondrial elongation, attenuated ferroptosis-mediated impairment of mitochondrial membrane potential, and stabilized iron trafficking and intracellular iron storage. In addition, Drp1 deficiency exerted metabolic effects, with reduced basal and maximal mitochondrial respiration and a metabolic shift towards glycolysis. These metabolic effects further alleviated the mitochondrial contribution to detrimental ROS production thereby significantly enhancing neural cell resilience against ferroptosis. Taken together, this study highlights the key role of Drp1 in mitochondrial pathways of ferroptosis and expose the regulator of mitochondrial dynamics as a potential therapeutic target in neurological diseases involving oxidative dysregulation.
    DOI:  https://doi.org/10.1038/s41419-024-07015-8
  2. Nat Commun. 2024 Aug 29. 15(1): 7463
    Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2.
    Rong-Hsuan Wang, Pin-Ru Chen, Yue-Ting Chen, Yi-Chang Chen, Yu-Hsin Chu, Chia-Chen Chien, Po-Chen Chien, Shao-Yun Lo, Zhong-Liang Wang, Min-Chen Tsou, Ssu-Yu Chen, Guang-Shen Chiu, Wen-Ling Chen, Yi-Hsuan Wu, Lily Hui-Ching Wang, Wen-Ching Wang, Shu-Yi Lin, Hsing-Jien Kung, Lu-Hai Wang, Hui-Chun Cheng, Kai-Ti Lin.
      Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H2S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism.
    DOI:  https://doi.org/10.1038/s41467-024-51875-9
  3. Nat Metab. 2024 Aug;6(8): 1529-1548
    The unique catalytic properties of PSAT1 mediate metabolic adaptation to glutamine blockade.
    Yijian Qiu, Olivia T Stamatatos, Qingting Hu, Jed Ruiter Swain, Suzanne Russo, Ava Sann, Ana S H Costa, Sara Violante, David L Spector, Justin R Cross, Michael J Lukey.
      Cultured cancer cells frequently rely on the consumption of glutamine and its subsequent hydrolysis by glutaminase (GLS). However, this metabolic addiction can be lost in the tumour microenvironment, rendering GLS inhibitors ineffective in the clinic. Here we show that glutamine-addicted breast cancer cells adapt to chronic glutamine starvation, or GLS inhibition, via AMPK-mediated upregulation of the serine synthesis pathway (SSP). In this context, the key product of the SSP is not serine, but α-ketoglutarate (α-KG). Mechanistically, we find that phosphoserine aminotransferase 1 (PSAT1) has a unique capacity for sustained α-KG production when glutamate is depleted. Breast cancer cells with resistance to glutamine starvation or GLS inhibition are highly dependent on SSP-supplied α-KG. Accordingly, inhibition of the SSP prevents adaptation to glutamine blockade, resulting in a potent drug synergism that suppresses breast tumour growth. These findings highlight how metabolic redundancy can be context dependent, with the catalytic properties of different metabolic enzymes that act on the same substrate determining which pathways can support tumour growth in a particular nutrient environment. This, in turn, has practical consequences for therapies targeting cancer metabolism.
    DOI:  https://doi.org/10.1038/s42255-024-01104-w
  4. Nat Rev Nephrol. 2024 Aug 28.
    Amino acid metabolism in kidney health and disease.
    Martine G E Knol, Vera C Wulfmeyer, Roman-Ulrich Müller, Markus M Rinschen.
      Amino acids form peptides and proteins and are therefore considered the main building blocks of life. The kidney has an important but under-appreciated role in the synthesis, degradation, filtration, reabsorption and excretion of amino acids, acting to retain useful metabolites while excreting potentially harmful and waste products from amino acid metabolism. A complex network of kidney transporters and enzymes guides these processes and moderates the competing concentrations of various metabolites and amino acid products. Kidney amino acid metabolism contributes to gluconeogenesis, nitrogen clearance, acid-base metabolism and provision of fuel for tricarboxylic acid cycle and urea cycle intermediates, and is thus a central hub for homeostasis. Conversely, kidney disease affects the levels and metabolism of a variety of amino acids. Here, we review the metabolic role of the kidney in amino acid metabolism and describe how different diseases of the kidney lead to aberrations in amino acid metabolism. Improved understanding of the metabolic and communication routes that are affected by disease could provide new mechanistic insights into the pathogenesis of kidney diseases and potentially enable targeted dietary or pharmacological interventions.
    DOI:  https://doi.org/10.1038/s41581-024-00872-8
  5. Nat Commun. 2024 Aug 27. 15(1): 7352
    Infection-induced peripheral mitochondria fission drives ER encapsulations and inter-mitochondria contacts that rescue bioenergetics.
    William A Hofstadter, Katelyn C Cook, Elene Tsopurashvili, Robert Gebauer, Vojtěch Pražák, Emily A Machala, Ji Woo Park, Kay Grünewald, Emmanuelle R J Quemin, Ileana M Cristea.
      The dynamic regulation of mitochondria shape via fission and fusion is critical for cellular responses to stimuli. In homeostatic cells, two modes of mitochondrial fission, midzone and peripheral, provide a decision fork between either proliferation or clearance of mitochondria. However, the relationship between specific mitochondria shapes and functions remains unclear in many biological contexts. While commonly associated with decreased bioenergetics, fragmented mitochondria paradoxically exhibit elevated respiration in several disease states, including infection with the prevalent pathogen human cytomegalovirus (HCMV) and metastatic melanoma. Here, incorporating super-resolution microscopy with mass spectrometry and metabolic assays, we use HCMV infection to establish a molecular mechanism for maintaining respiration within a fragmented mitochondria population. We establish that HCMV induces fragmentation through peripheral mitochondrial fission coupled with suppression of mitochondria fusion. Unlike uninfected cells, the progeny of peripheral fission enter mitochondria-ER encapsulations (MENCs) where they are protected from degradation and bioenergetically stabilized during infection. MENCs also stabilize pro-viral inter-mitochondria contacts (IMCs), which electrochemically link mitochondria and promote respiration. Demonstrating a broader relevance, we show that the fragmented mitochondria within metastatic melanoma cells also form MENCs. Our findings establish a mechanism where mitochondria fragmentation can promote increased respiration, a feature relevant in the context of human diseases.
    DOI:  https://doi.org/10.1038/s41467-024-51680-4
  6. Metabolites. 2024 Aug 06. pii: 435. [Epub ahead of print]14(8):
    Metabolic and Oxidative Stress Management Heterogeneity in a Panel of Breast Cancer Cell Lines.
    Paola Maycotte, Fabiola Lilí Sarmiento-Salinas, Alin García-Miranda, Cesar Ivan Ovando-Ovando, Diana Xochiquetzal Robledo-Cadena, Luz Hernández-Esquivel, Ricardo Jasso-Chávez, Alvaro Marín-Hernández.
      Metabolic alterations are recognized as one of the hallmarks of cancer. Among these, alterations in mitochondrial function have been associated with an enhanced production of Reactive Oxygen Species (ROS), which activate ROS-regulated cancer cell signaling pathways. Breast cancer is the main cancer-related cause of death for women globally. It is a heterogeneous disease with subtypes characterized by specific molecular features and patient outcomes. With the purpose of identifying differences in energy metabolism and the oxidative stress management system in non-tumorigenic, estrogen receptor positive (ER+) and triple negative (TN) breast cancer cells, we evaluated ROS production, protein enzyme levels and activities and profiled energy metabolism. We found differences in energetic metabolism and ROS management systems between non-tumorigenic and cancer cells and between ER+ and TN breast cancer cells. Our results indicate a dependence on glycolysis despite different glycolytic ATP levels in all cancer cell lines tested. In addition, our data show that high levels of ROS in TN cells are a result of limited antioxidant capacity in the NADPH producing and GSH systems, mitochondrial dysfunction and non-mitochondrial ROS production, making them more sensitive to GSH synthesis inhibitors. Our data suggest that metabolic and antioxidant profiling of breast cancer will provide important targets for metabolic inhibitors or antioxidant treatments for breast cancer therapy.
    Keywords:  antioxidant system; breast cancer; energy metabolism; reactive oxygen species
    DOI:  https://doi.org/10.3390/metabo14080435
  7. Nature. 2024 Aug 23.
    Lactate helps cancer cells resist chemotherapy.
      
    Keywords:  Cancer; Metabolism
    DOI:  https://doi.org/10.1038/d41586-024-02731-9
  8. Cell Metab. 2024 Aug 13. pii: S1550-4131(24)00326-7. [Epub ahead of print]
    Mitochondrial membrane lipids in the regulation of bioenergetic flux.
    Stephen Thomas Decker, Katsuhiko Funai.
      Oxidative phosphorylation (OXPHOS) occurs through and across the inner mitochondrial membrane (IMM). Mitochondrial membranes contain a distinct lipid composition, aided by lipid biosynthetic machinery localized in the IMM and class-specific lipid transporters that limit lipid traffic in and out of mitochondria. This unique lipid composition appears to be essential for functions of mitochondria, particularly OXPHOS, by its effects on direct lipid-to-protein interactions, membrane properties, and cristae ultrastructure. This review highlights the biological significance of mitochondrial lipids, with a particular spotlight on the role of lipids in mitochondrial bioenergetics. We describe pathways for the biosynthesis of mitochondrial lipids and provide evidence for their roles in physiology, their implications in human disease, and the mechanisms by which they regulate mitochondrial bioenergetics.
    Keywords:  bioenergetics; mitochondria; phospholipids
    DOI:  https://doi.org/10.1016/j.cmet.2024.07.024
  9. Nat Commun. 2024 Aug 25. 15(1): 7323
    Structural basis for allosteric regulation of human phosphofructokinase-1.
    Eric M Lynch, Heather Hansen, Lauren Salay, Madison Cooper, Stepan Timr, Justin M Kollman, Bradley A Webb.
      Phosphofructokinase-1 (PFK1) catalyzes the rate-limiting step of glycolysis, committing glucose to conversion into cellular energy. PFK1 is highly regulated to respond to the changing energy needs of the cell. In bacteria, the structural basis of PFK1 regulation is a textbook example of allostery; molecular signals of low and high cellular energy promote transition between an active R-state and inactive T-state conformation, respectively. Little is known, however, about the structural basis for regulation of eukaryotic PFK1. Here, we determine structures of the human liver isoform of PFK1 (PFKL) in the R- and T-state by cryoEM, providing insight into eukaryotic PFK1 allosteric regulatory mechanisms. The T-state structure reveals conformational differences between the bacterial and eukaryotic enzyme, the mechanisms of allosteric inhibition by ATP binding at multiple sites, and an autoinhibitory role of the C-terminus in stabilizing the T-state. We also determine structures of PFKL filaments that define the mechanism of higher-order assembly and demonstrate that these structures are necessary for higher-order assembly of PFKL in cells.
    DOI:  https://doi.org/10.1038/s41467-024-51808-6
  10. Nat Commun. 2024 Aug 23. 15(1): 7254
    An economic demand-based framework for prioritization strategies in response to transient amino acid limitations.
    Ritu Gupta, Swagata Adhikary, Nidhi Dalpatraj, Sunil Laxman.
      Cells contain disparate amounts of distinct amino acids, each of which has different metabolic and chemical origins, but the supply cost vs demand requirements of each is unclear. Here, using yeast we quantify the restoration-responses after disrupting amino acid supply, and uncover a hierarchically prioritized restoration strategy for distinct amino acids. We comprehensively calculate individual amino acid biosynthetic supply costs, quantify total demand for an amino acid, and estimate cumulative supply/demand requirements for each amino acid. Through this, we discover that the restoration priority is driven by the gross demand for an amino acid, which is itself coupled to low supply costs for that amino acid. Demand from metabolic requirements dominate the demand-pulls for an amino acid, as exemplified by the largest restoration response upon disrupting arginine supply. Collectively, this demand-driven framework that drives the amino acid economy can identify novel amino acid responses, and help design metabolic engineering applications.
    DOI:  https://doi.org/10.1038/s41467-024-51769-w
  11. Sci Rep. 2024 08 24. 14(1): 19673
    Detailed analysis of Mdivi-1 effects on complex I and respiratory supercomplex assembly.
    Nico Marx, Nadine Ritter, Paul Disse, Guiscard Seebohm, Karin B Busch.
      Several human diseases, including cancer and neurodegeneration, are associated with excessive mitochondrial fragmentation. In this context, mitochondrial division inhibitor (Mdivi-1) has been tested as a therapeutic to block the fission-related protein dynamin-like protein-1 (Drp1). Recent studies suggest that Mdivi-1 interferes with mitochondrial bioenergetics and complex I function. Here we show that the molecular mechanism of Mdivi-1 is based on inhibition of complex I at the IQ site. This leads to the destabilization of complex I, impairs the assembly of N- and Q-respirasomes, and is associated with increased ROS production and reduced efficiency of ATP generation. Second, the calcium homeostasis of cells is impaired, which for example affects the electrical activity of neurons. Given the results presented here, a potential therapeutic application of Mdivi-1 is challenging because of its potential impact on synaptic activity. Similar to the Complex I inhibitor rotenone, Mdivi-1 may lead to neurodegenerative effects in the long term.
    Keywords:  Calcium metabolism; Inhibition; Mdivi-1; Mitochondria; Neuronal activity; Respiratory complex I; Respiratory supercomplexes
    DOI:  https://doi.org/10.1038/s41598-024-69748-y
  12. Cell Stem Cell. 2024 Aug 21. pii: S1934-5909(24)00285-6. [Epub ahead of print]
    Mitochondrial serine catabolism safeguards maintenance of the hematopoietic stem cell pool in homeostasis and injury.
    Changhong Du, Chaonan Liu, Kuan Yu, Shuzhen Zhang, Zeyu Fu, Xinliang Chen, Weinian Liao, Jun Chen, Yimin Zhang, Xinmiao Wang, Mo Chen, Fang Chen, Mingqiang Shen, Cheng Wang, Shilei Chen, Song Wang, Junping Wang.
      Hematopoietic stem cells (HSCs) employ a very unique metabolic pattern to maintain themselves, while the spectrum of their metabolic adaptations remains incompletely understood. Here, we uncover a distinct and heterogeneous serine metabolism within HSCs and identify mouse HSCs as a serine auxotroph whose maintenance relies on exogenous serine and the ensuing mitochondrial serine catabolism driven by the hydroxymethyltransferase 2 (SHMT2)-methylene-tetrahydrofolate dehydrogenase 2 (MTHFD2) axis. Mitochondrial serine catabolism primarily feeds NAD(P)H generation to maintain redox balance and thereby diminishes ferroptosis susceptibility of HSCs. Dietary serine deficiency, or genetic or pharmacological inhibition of the SHMT2-MTHFD2 axis, increases ferroptosis susceptibility of HSCs, leading to impaired maintenance of the HSC pool. Moreover, exogenous serine protects HSCs from irradiation-induced myelosuppressive injury by fueling mitochondrial serine catabolism to mitigate ferroptosis. These findings reframe the canonical view of serine from a nonessential amino acid to an essential niche metabolite for HSC pool maintenance.
    Keywords:  NADPH; SHMT2; ferroptosis; hematopoietic stem cell; heterogeneity; ionizing radiation; mitochondrial serine catabolism; myelosuppressive injury
    DOI:  https://doi.org/10.1016/j.stem.2024.07.009
  13. Nat Cardiovasc Res. 2024 May;3(5): 500-514
    Mitochondrial calcium uniporter channel gatekeeping in cardiovascular disease.
    Tyler L Stevens, Henry M Cohen, Joanne F Garbincius, John W Elrod.
      The mitochondrial calcium (mCa2+) uniporter channel (mtCU) resides at the inner mitochondrial membrane and is required for Ca2+ to enter the mitochondrial matrix. The mtCU is essential for cellular function, as mCa2+ regulates metabolism, bioenergetics, signaling pathways and cell death. mCa2+ uptake is primarily regulated by the MICU family (MICU1, MICU2, MICU3), EF-hand-containing Ca2+-sensing proteins, which respond to cytosolic Ca2+ concentrations to modulate mtCU activity. Considering that mitochondrial function and Ca2+ signaling are ubiquitously disrupted in cardiovascular disease, mtCU function has been a hot area of investigation for the last decade. Here we provide an in-depth review of MICU-mediated regulation of mtCU structure and function, as well as potential mtCU-independent functions of these proteins. We detail their role in cardiac physiology and cardiovascular disease by highlighting the phenotypes of different mutant animal models, with an emphasis on therapeutic potential and targets of interest in this pathway.
    DOI:  https://doi.org/10.1038/s44161-024-00463-7
  14. Autophagy. 2024 Aug 23.
    Function of CSNK2/CK2 selectively affects the endoplasmic reticulum and the Golgi apparatus in mtor-mediated autophagy induction.
    Pablo Sanz-Martinez, Rayene Berkane, Alexandra Stolz.
      Selective macroautophagy/autophagy of the endoplasmic reticulum, known as reticulophagy/ER-phagy, is essential to maintain ER homeostasis. We recently showed that members of the autophagy receptor family RETREG/FAM134 are regulated by phosphorylation-dependent ubiquitination. In an unbiased screen we had identified several kinases downstream of MTOR with profound impact on reticulophagy flux, including ATR and CSNK2/CK2. Inhibition of CSNK2 by SGC-CK2-1 prevented regulatory ubiquitination of RETREG1/FAM134B and RETREG3/FAM134C upon autophagy activation as well as the formation of high-density RETREG1- and RETREG3-clusters. Here we report on additional resource data of global proteomics upon CSNK2 and ATR inhibition, respectively. Our data suggests that the function of CSNK2 is mainly limited to the ER/reticulophagy and Golgi/Golgiphagy, while ATR inhibition by VE-822 affects the vast majority of organelles/selective autophagy pathways.
    Keywords:  Kinase signaling; LAMP1; RETREG; methuosis; selective autophagy; vacuolization
    DOI:  https://doi.org/10.1080/15548627.2024.2395725
  15. J Cell Biol. 2024 Nov 04. pii: e202308099. [Epub ahead of print]223(11):
    Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.
    Yewei Huang, Gan Luo, Kesong Peng, Yue Song, Yusha Wang, Hongtao Zhang, Jin Li, Xiangmin Qiu, Maomao Pu, Xinchang Liu, Chao Peng, Dante Neculai, Qiming Sun, Tianhua Zhou, Pintong Huang, Wei Liu.
      The transcription factor TFEB is a major regulator of lysosomal biogenesis and autophagy. There is growing evidence that posttranslational modifications play a crucial role in regulating TFEB activity. Here, we show that lactate molecules can covalently modify TFEB, leading to its lactylation and stabilization. Mechanically, lactylation at K91 prevents TFEB from interacting with E3 ubiquitin ligase WWP2, thereby inhibiting TFEB ubiquitination and proteasome degradation, resulting in increased TFEB activity and autophagy flux. Using a specific antibody against lactylated K91, enhanced TFEB lactylation was observed in clinical human pancreatic cancer samples. Our results suggest that lactylation is a novel mode of TFEB regulation and that lactylation of TFEB may be associated with high levels of autophagy in rapidly proliferating cells, such as cancer cells.
    DOI:  https://doi.org/10.1083/jcb.202308099
  16. Sheng Li Xue Bao. 2024 Aug 25. 76(4): 576-586
    [Molecular mechanism of CDO1 regulating common metabolic diseases].
    Qi Liu, Wen-Qing Shen.
      Cysteine dioxygenase type 1 (CDO1) belongs to the cysteine dioxygenase (CDO) family. CDO1 is the key enzyme in cysteine catabolism and taurine synthesis. CDO1 is highly expressed in liver, adipose tissue, pancreas, kidney, lung, brain and small intestine. CDO1 is involved in the pathophysiological regulation of various common metabolic diseases, such as lipid metabolism disorders, insulin resistance, obesity, tumors/cancers, and neurodegenerative diseases. This article summarizes the research progress on the molecular mechanisms of CDO1 regulation of common metabolic diseases in recent years, aiming to provide new theoretical and practical basis for CDO1-targeted therapy for insulin resistance, obesity, tumors/cancers, and neurodegenerative diseases.
  17. Cell Immunol. 2024 Aug 26. pii: S0008-8749(24)00067-4. [Epub ahead of print]403-404 104864
    The role of mitochondrial fusion and fission in immune-mediated inflammatory diseases.
    Yulai Fang, Shichen Min, Hong Shen.
      Mitochondria are highly dynamic organelles that maintain their homeostasis through mitochondrial dynamics. Mitochondrial fusion and fission are two important processes of mitochondrial dynamics. There is accumulating evidence that mitochondrial fusion and fission play an important role in the development of immune-mediated inflammatory diseases. This article provides a brief review of the essential role of mitochondrial fusion and fission in immune-mediated inflammatory diseases. It will provide a novel perspective and direction for the elucidation of the pathogenesis and treatment of immune-mediated inflammatory diseases.
    Keywords:  Immune-mediated inflammatory diseases; Mitochondrial fission; Mitochondrial fusion
    DOI:  https://doi.org/10.1016/j.cellimm.2024.104864
  18. Trends Endocrinol Metab. 2024 Aug 23. pii: S1043-2760(24)00190-5. [Epub ahead of print]
    Exploring the heterogeneous targets of metabolic aging at single-cell resolution.
    Shuhui Sun, Mengmeng Jiang, Shuai Ma, Jie Ren, Guang-Hui Liu.
      Our limited understanding of metabolic aging poses major challenges to comprehending the diverse cellular alterations that contribute to age-related decline, and to devising targeted interventions. This review provides insights into the heterogeneous nature of cellular metabolism during aging and its response to interventions, with a specific focus on cellular heterogeneity and its implications. By synthesizing recent findings using single-cell approaches, we explored the vulnerabilities of distinct cell types and key metabolic pathways. Delving into the cell type-specific alterations underlying the efficacy of systemic interventions, we also discuss the complexity of integrating single-cell data and advocate for leveraging computational tools and artificial intelligence to harness the full potential of these data, develop effective strategies against metabolic aging, and promote healthy aging.
    Keywords:  aging; heterogeneity; intervention; metabolism; single-cell
    DOI:  https://doi.org/10.1016/j.tem.2024.07.009
This page is being maintained by Thomas Krichel. It was last updated on 2024‒09‒02 at 12:01.