Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge
Open accessAbstract
Brown adipose tissue (BAT) is a specialized thermogenic organ in mammals. The ability of BAT mitochondria to generate heat in response to cold-challenge to maintain core body temperature is essential for organismal survival. While cold activated BAT mitochondrial biogenesis is recognized as critical for thermogenic adaptation, the contribution of mitochondrial quality control to this process remains unclear. Here, we show mitophagy is required for brown adipocyte mitochondrial homeostasis during thermogenic adaptation. Mitophagy is significantly increased in BAT from cold-challenged mice (4 °C) and in β-agonist treated brown adipocytes. Blockade of mitophagy compromises brown adipocytes mitochondrial oxidative phosphorylation (OX-PHOS) capacity, as well as BAT mitochondrial integrity. Mechanistically, cold-challenge induction of BAT mitophagy is UCP1-dependent. Furthermore, our results indicate that mitophagy coordinates with mitochondrial biogenesis, maintaining activated BAT mitochondrial homeostasis. Collectively, our in vivo and in vitro findings identify mitophagy as critical for brown adipocyte mitochondrial homeostasis during cold adaptation.
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Autophagy and mitophagy flows are attenuated in Ucp1-/- murine brown adipocytes.
“The importance of mitochondrial uncoupling in mitophagy activation is illustrated by the attenuation of autophagy and mitophagy flows in Ucp1-/- murine brown adipocytes [109].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [109]
Mitophagy seems to be continuously activated in brown adipocytes.
“In addition, mitophagy also seems to be continuously activated in brown adipocytes, possibly in order to degrade dysfunctional mitochondria exposed to prolonged mitochondrial uncoupling (and possible damages induced by oxidative stress) [109].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [109]
Continuous mitophagy in brown adipocytes may serve to degrade dysfunctional mitochondria exposed to prolonged mitochondrial uncoupling and oxidative stress.
“In addition, mitophagy also seems to be continuously activated in brown adipocytes, possibly in order to degrade dysfunctional mitochondria exposed to prolonged mitochondrial uncoupling (and possible damages induced by oxidative stress) [109].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [109]
Mitochondrial uncoupling is important for mitophagy activation.
“The importance of mitochondrial uncoupling in mitophagy activation is illustrated by the attenuation of autophagy and mitophagy flows in Ucp1-/- murine brown adipocytes [109].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [109]
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Multifaceted mitochondrial quality control in brown adipose tissue
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Oleanolic acid induces HCT116 colon cancer cell death through the p38/FOXO3a/Sirt6 pathway
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SIRT5 Inhibition Induces Brown Fat-Like Phenotype in 3T3-L1 Preadipocytes
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Thermogenesis and Energy Metabolism in Brown Adipose Tissue in Animals Experiencing Cold Stress
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Cold exposure alters lipid metabolism of skeletal muscle through HIF-1α-induced mitophagy
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Inappropriate Intrusion of an Axonal Mitochondrial Anchor into Dendrites Causes Neurodegeneration
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Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes
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Links Between Autophagy and Healthy Aging
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Self-citationSEL1L–HRD1 ERAD–autophagy interplay maintains mitochondrial homeostasis in brown adipocytes
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Nonanoic acid and cholecystokinin induce beige adipogenesis
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Food-Derived Peptides as Potential Modulators of Mitophagy
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Rôle des flux de lactate dans le métabolisme des tissus adipeux beiges et bruns
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- Authors
- Lu, Y., Fujioka, H., Joshi, D., Li, Q., Sangwung, P., Hsieh, P., Zhu, J., Torio, J., Sweet, D., Wang, L., Chiu, S. Y., Croniger, C., Liao, X., & Jain, M. K.
- Affiliations
- University Hospitals of Cleveland (US)
- Case Western Reserve University (US)
- University of Wisconsin–Madison (US)
- Capital Medical University (CN)
- Illinois Mathematics and Science Academy (US)
- Corresponding author
- Lu, Yuan
- Jain, Mukesh K.
- ORCID
- Venue
- Scientific Reports
- Published
- 2018-05-29
- Volume
- 8
- Issue
- 1
- Pages
- 8251-8251
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5974273
- OpenAlex
- W2807640547
- Cited by
- 76
- References
- 74
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 11 · 2023: 13 · 2022: 8 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 1
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- American Heart Association (R01HL119195)
- National Institutes of Health
- National Institute on Aging (F30AG054237)
- National Heart, Lung, and Blood Institute (F30HL139014, R35HL135789, R01HL086548, R01HL119195, R01HL123098)
- National Institute of General Medical Sciences (T32GM007250)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK111468)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitophagy, brown adipose tissue, mitochondrial homeostasis, cold adaptation, thermogenesis, mitochondrial biogenesis, UCP1, oxidative phosphorylation, mitochondrial quality control, beta-adrenergic agonists, brown adipocytes
- MeSH terms
- Uncoupling Protein 1, Adrenergic beta-Agonists, Animals, Organelle Biogenesis, Adipose Tissue, Brown, Cells, Cultured, Cold Temperature, Homeostasis, Hypothermia, Mice, Inbred C57BL, Mitochondria, Oxidative Phosphorylation, Adipocytes, Mice, Knockout, Thermogenesis, Mice, Mitophagy
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