Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism

Mitochondria are essential for cellular energy production and are implicated in numerous diseases, including diabetic kidney disease (DKD). Current evidence indicates that mitochondrial dysfunction results in alterations in several metabolic pathways within kidney cells, thereby contributing to the...

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Main Authors: Phoom Narongkiatikhun, Ye Ji Choi, Hailey Hampson, Jimmy Gotzamanis, Guanshi Zhang, Daniel H. van Raalte, Ian H. de Boer, Robert G. Nelson, Kalie L. Tommerdahl, Phillip J. McCown, Jenny Kanter, Kumar Sharma, Petter Bjornstad, Pierre Jean Saulnier
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924019478
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author Phoom Narongkiatikhun
Ye Ji Choi
Hailey Hampson
Jimmy Gotzamanis
Guanshi Zhang
Daniel H. van Raalte
Ian H. de Boer
Robert G. Nelson
Kalie L. Tommerdahl
Phillip J. McCown
Jenny Kanter
Kumar Sharma
Petter Bjornstad
Pierre Jean Saulnier
author_facet Phoom Narongkiatikhun
Ye Ji Choi
Hailey Hampson
Jimmy Gotzamanis
Guanshi Zhang
Daniel H. van Raalte
Ian H. de Boer
Robert G. Nelson
Kalie L. Tommerdahl
Phillip J. McCown
Jenny Kanter
Kumar Sharma
Petter Bjornstad
Pierre Jean Saulnier
author_sort Phoom Narongkiatikhun
collection DOAJ
description Mitochondria are essential for cellular energy production and are implicated in numerous diseases, including diabetic kidney disease (DKD). Current evidence indicates that mitochondrial dysfunction results in alterations in several metabolic pathways within kidney cells, thereby contributing to the progression of DKD. Furthermore, mitochondrial dysfunction can engender an inflammatory milieu, leading to the activation and recruitment of immune cells to the kidney tissue, potentially perturbing intrarenal metabolism. In addition, this inflammatory microenvironment has the potential to modify immune cell metabolism, which may further accentuate the immune-mediated kidney injury. This understanding has led to the emerging field of immunometabolism, which views DKD as not just a metabolic disorder caused by hyperglycemia but also one with significant immune contributions. Targeting mitochondrial function and immunometabolism may offer protective effects for the kidneys, complementing current therapies and potentially mitigating the risk of DKD progression. This comprehensive review examines the impact of mitochondrial dysfunction and the potential role of immunometabolism in DKD. We also discuss tools for investigating these mechanisms and propose avenues for integrating this research with existing therapies. These insights underscore the modulation of mitochondrial function and immunometabolism as a critical strategy for decelerating DKD progression.
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publishDate 2024-12-01
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series Kidney International Reports
spelling doaj-art-b8b3c12d3e7844bdad0228e80f92ec3a2025-08-20T03:21:18ZengElsevierKidney International Reports2468-02492024-12-019123386340210.1016/j.ekir.2024.09.019Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and ImmunometabolismPhoom Narongkiatikhun0Ye Ji Choi1Hailey Hampson2Jimmy Gotzamanis3Guanshi Zhang4Daniel H. van Raalte5Ian H. de Boer6Robert G. Nelson7Kalie L. Tommerdahl8Phillip J. McCown9Jenny Kanter10Kumar Sharma11Petter Bjornstad12Pierre Jean Saulnier13Division of Endocrinology, Department of Medicine, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USA; Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Correspondence: Phoom Narongkiatikhun, Division of Endocrinology, Department of Medicine, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USA.Department of Pediatrics, Section of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, Colorado, USADivision of Endocrinology, Department of Medicine, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USAINSERM Centre d’Investigation Clinique 1402, CHU Poitiers, University of Poitiers, Poitiers, FranceDepartment of Medicine, Section of Nephrology, University of Texas Health San Antonio, San Antonio, Texas, USADiabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, The NetherlandsDivision of Nephrology, University of Washington School of Medicine, Seattle, Washington, USAChronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USADivision of Endocrinology, Department of Medicine, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USADepartment of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, Michigan, USADivision of Endocrinology, Department of Medicine, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USADepartment of Medicine, Section of Nephrology, University of Texas Health San Antonio, San Antonio, Texas, USADivision of Endocrinology, Department of Medicine, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USAINSERM Centre d’Investigation Clinique 1402, CHU Poitiers, University of Poitiers, Poitiers, FranceMitochondria are essential for cellular energy production and are implicated in numerous diseases, including diabetic kidney disease (DKD). Current evidence indicates that mitochondrial dysfunction results in alterations in several metabolic pathways within kidney cells, thereby contributing to the progression of DKD. Furthermore, mitochondrial dysfunction can engender an inflammatory milieu, leading to the activation and recruitment of immune cells to the kidney tissue, potentially perturbing intrarenal metabolism. In addition, this inflammatory microenvironment has the potential to modify immune cell metabolism, which may further accentuate the immune-mediated kidney injury. This understanding has led to the emerging field of immunometabolism, which views DKD as not just a metabolic disorder caused by hyperglycemia but also one with significant immune contributions. Targeting mitochondrial function and immunometabolism may offer protective effects for the kidneys, complementing current therapies and potentially mitigating the risk of DKD progression. This comprehensive review examines the impact of mitochondrial dysfunction and the potential role of immunometabolism in DKD. We also discuss tools for investigating these mechanisms and propose avenues for integrating this research with existing therapies. These insights underscore the modulation of mitochondrial function and immunometabolism as a critical strategy for decelerating DKD progression.http://www.sciencedirect.com/science/article/pii/S2468024924019478diabetic kidney diseaseimmunometabolismmetabolic reprogrammingmitochondrial dysfunctionoxidative phosphorylation
spellingShingle Phoom Narongkiatikhun
Ye Ji Choi
Hailey Hampson
Jimmy Gotzamanis
Guanshi Zhang
Daniel H. van Raalte
Ian H. de Boer
Robert G. Nelson
Kalie L. Tommerdahl
Phillip J. McCown
Jenny Kanter
Kumar Sharma
Petter Bjornstad
Pierre Jean Saulnier
Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism
Kidney International Reports
diabetic kidney disease
immunometabolism
metabolic reprogramming
mitochondrial dysfunction
oxidative phosphorylation
title Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism
title_full Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism
title_fullStr Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism
title_full_unstemmed Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism
title_short Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism
title_sort unraveling diabetic kidney disease the roles of mitochondrial dysfunction and immunometabolism
topic diabetic kidney disease
immunometabolism
metabolic reprogramming
mitochondrial dysfunction
oxidative phosphorylation
url http://www.sciencedirect.com/science/article/pii/S2468024924019478
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