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The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4
Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee
Diabetes Metab J. 2023;47(2):153-163.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0305
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AbstractAbstract PDFPubReader   ePub   
Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.

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  • From aging to space: A comparative biology of skeletal muscle degeneration
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  • High-concentration Mg2+ stress improves L-lactic acid biosynthesis of Bacillus coagulans revealed by combined analysis of transcriptome and metabolome
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    Journal of Biotechnology.2026; 409: 1.     CrossRef
  • PDK4 is critical for metabolic regulation and progesterone production in bovine granulosa cells
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    Biology of Reproduction.2026; 114(3): 952.     CrossRef
  • Targeting PDK4 attenuates neointimal hyperplasia and regulates VSMC phenotypic switching, apoptosis, and autophagy
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    Biochemical Pharmacology.2026; 247: 117805.     CrossRef
  • Multi-dimensional analysis reveals the potential of PDK4 as a tumor biomarker and target for immunotherapy
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    Discover Oncology.2026;[Epub]     CrossRef
  • Research progress on the molecular mechanism and clinical evidence of glucagon-like peptide-1 receptor agonists in improving sarcopenia
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    Diabetology & Metabolic Syndrome.2026;[Epub]     CrossRef
  • Efficacy of thiamine (vitamin B1) in sepsis and septic shock: A meta-analysis of randomized controlled trials
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    Clinics.2026; 81: 100901.     CrossRef
  • Mitochondrial ROS dyshomeostasis: a key driver of accelerated supraspinatus atrophy after rotator cuff injury
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    Frontiers in Physiology.2026;[Epub]     CrossRef
  • Molecular and Cellular Mechanisms of Sarcopenia: Integrating Fiber‐Type Remodeling, Contractile Protein Dynamics, and Systemic Regulatory Pathways
    Nikam Rutuja Dilesh, Divyansh Khatri, Richa Shrivastava, Sapana Kushwaha
    Cell Biochemistry and Function.2026;[Epub]     CrossRef
  • Targeting the activin/myostatin - actrii pathway to preserve skeletal muscle mass in obesity: mechanistic insights and therapeutic perspectives
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    Reviews in Endocrine and Metabolic Disorders.2026;[Epub]     CrossRef
  • Repairing muscle with broccoli-derived sulforaphane: A preclinical evaluation for the treatment of mitochondrial myopathies
    Thomas Lilley, Donny M. Camera, Faith A.A. Kwa
    Drug Discovery Today.2025; 30(1): 104283.     CrossRef
  • Could Sarcopenia Be Related to Chemotherapy in Gastrointestinal Cancer? A Cross-Sectional Study Including Comprehensive Geriatric Assessment
    Kamile Sılay, Gökhan Uçar, Tülay Eren, Hande Selvi Öztorun, Ozan Yazıcı, Nuriye Özdemir
    Journal of Clinical Medicine.2025; 14(3): 711.     CrossRef
  • The association of body roundness index and body mass index with frailty and all-cause mortality: a study from the population aged 40 and above in the United States
    Jianqiang Zhang, Huifeng Zhang
    Lipids in Health and Disease.2025;[Epub]     CrossRef
  • Near Infrared‐Mediated Intracellular NADH Delivery Strengthens Mitochondrial Function and Stability in Muscle Dysfunction Model
    Hui Bang Cho, Hye‐Ryoung Kim, Sujeong Lee, Chae Won Cho, Ji‐In Park, Seulki Youn, Gyuwon So, Sumin Kang, Hye Jin Kim, Keun‐Hong Park
    Advanced Science.2025;[Epub]     CrossRef
  • The Association Between Low Muscle Mass and the Risk of Depressive Symptoms: A Cross‐Sectional Study Based on the Chinese Longitudinal Health Longevity Survey (CLHLS)
    Yuting Yang, Yan Wang, Qiao Chen, Ling Li, Wangping Jia
    Brain and Behavior.2025;[Epub]     CrossRef
  • Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies
    Xiangyuan Meng, Hui Zhang, Zhenhu Zhao, Siyao li, Xin Zhang, Ruihan Guo, Huimin Liu, Yiling Yuan, Wanrui Li, Qi Song, Jinyu Liu
    Molecular Medicine.2025;[Epub]     CrossRef
  • Dipalmitoylphosphatidylcholine Lipid Vesicles for Delivering HMB, NMN, and L-Leucine in Sarcopenia Therapy
    Alfred Najm, Alexandra Cătălina Bîrcă, Adelina-Gabriela Niculescu, Adina Alberts, Alexandru Mihai Grumezescu, Bianca Gălățeanu, Bogdan Ștefan Vasile, Mircea Beuran, Bogdan Severus Gaspar, Ariana Hudiță
    Molecules.2025; 30(7): 1437.     CrossRef
  • Renometabolic disorder in experimental rat model of polycystic ovarian syndrome is reversed by acetate-mediated inhibition of pyruvate dehydrogenase kinase 4
    Stephanie E. Areloegbe, Chukwubueze L. Atuma, Ayodeji Aturamu, Isaac O. Ajadi, Oluseyi E. Adelekan, Mary B. Ajadi, Christopher O. Akintayo, Gloria O. Omoruyi, Samuel O. Onyekweli, Omosola F. Anifowose, Oluwatobi A. Amusa, Kayode Ajayi, Paul A. Oyewole, To
    BMC Nephrology.2025;[Epub]     CrossRef
  • Unraveling the Metabolic Pathways Between Metabolic-Associated Fatty Liver Disease (MAFLD) and Sarcopenia
    Marina Ribas Losasso, Maria Luiza Cesto Parussolo, Antony Oliveira Silva, Rosa Direito, Karina Quesada, Claudia Rucco Penteado Detregiachi, Marcelo Dib Bechara, Nahum Méndez-Sánchez, Ludovico Abenavoli, Adriano Cressoni Araújo, Ricardo de Alvares Goulart,
    International Journal of Molecular Sciences.2025; 26(10): 4673.     CrossRef
  • Mechanisms of aristolochic acid I Hepatotoxicity: Central role of PDK4-Induced mitochondrial dysfunction and hepatic inflammation
    Zhaobin Wang, Kunyang Li, Xiaoqi Yi, Yichen Wu, Yang Zhao, Pingping He, Qinghua Zeng, Enxiang Zhang
    Food and Chemical Toxicology.2025; 203: 115592.     CrossRef
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    EMBO Molecular Medicine.2025; 17(7): 1599.     CrossRef
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    Genes.2025; 16(7): 814.     CrossRef
  • Therapeutic advances in sarcopenia management: From traditional interventions to personalized medicine
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    Clinical Nutrition.2025; 51: 187.     CrossRef
  • An in vitro model to study molecular pathogenesis of sarcopenia established by a SASP-dependent human myotube culture
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    PLOS One.2025; 20(7): e0326968.     CrossRef
  • Postbiotic Intervention in Sarcopenia: The Role of Lactiplantibacillus plantarum HY7715 and Its Extracellular Vesicles
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    Life.2025; 15(7): 1101.     CrossRef
  • Targeting ALDH2 to promote skeletal muscle health: A novel strategy against mitochondrial dysfunction
    Katia S. G. Andrade, Jianming Liu, Dimitrius Santiago P. S. F. Guimarães, Julio C.B. Ferreira, Zhigao Wang, Da‐Zhi Wang, Leonardo R. Silveira
    The Journal of Physiology.2025; 603(16): 4483.     CrossRef
  • Healthy Dietary Patterns and Risk of Sarcopenia in Adults Aged > 50 Years: A Systematic Review and Meta-Analysis Considering EWGSOP1 and EWGSOP2 Criteria
    Roxana E. Ruiz-Valenzuela, Reyes Artacho, María Dolores Ruiz-López, Esther Molina-Montes
    Nutrients.2025; 17(17): 2764.     CrossRef
  • The Role of Methylmalonic Acid in the Risk of Sarcopenia and All‐Cause Mortality Among Individuals With Sarcopenia: Evidence From NHANES
    Ping Zhu, Jie Zhang, Xue‐Chun Liu, Ming Song, Bin Lu, Zhi‐Cheng Yang, Hui Pan, Ya‐Qiong Jiao, Ya‐Fei Guo, Fang‐Fang Chen, Zhi‐Hao Wang, Bo‐Ang Hu, Ming Zhong
    Food Science & Nutrition.2025;[Epub]     CrossRef
  • Mechanical Stimulation Induces Yap Mediated OCTN2 Transcription to Enhance Carnitine Metabolism in Sarcopenia
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    Journal of Cachexia, Sarcopenia and Muscle.2025;[Epub]     CrossRef
  • Skeletal muscle alterations in type 2 diabetes mellitus with and without dyslipidemia
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    Lipids in Health and Disease.2025;[Epub]     CrossRef
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    Journal of Translational Medicine.2025;[Epub]     CrossRef
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    EMBO Molecular Medicine.2025; 17(12): 3607.     CrossRef
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