Spermidine deficiency induces BNIP3/LC3B-mediated mitophagy in the salivary glands of accelerated aging mice.
| Title: | Spermidine deficiency induces BNIP3/LC3B-mediated mitophagy in the salivary glands of accelerated aging mice. |
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| Authors: | Toan NK; Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA.; Duong MD; Department of Pathology, School of Dentistry, Chosun University, Gwangju 61452, Republic of Korea.; Phu ND; Department of Pathology, School of Dentistry, Chosun University, Gwangju 61452, Republic of Korea.; Thanh LV; Department of Pathology, School of Dentistry, Chosun University, Gwangju 61452, Republic of Korea.; Ahn SG; Department of Pathology, School of Dentistry, Chosun University, Gwangju 61452, Republic of Korea. Electronic address: ahnsg@chosun.ac.kr. |
| Source: | Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2026 Feb; Vol. 1870 (2), pp. 130897. Date of Electronic Publication: 2025 Dec 16. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731726 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8006 (Electronic) Linking ISSN: 03044165 NLM ISO Abbreviation: Biochim Biophys Acta Gen Subj Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier |
| MeSH Terms: | Spermidine*/metabolism ; Salivary Glands*/metabolism ; Salivary Glands*/pathology ; Microtubule-Associated Proteins*/metabolism ; Microtubule-Associated Proteins*/genetics ; Aging*/metabolism ; Membrane Proteins*/metabolism ; Membrane Proteins*/genetics ; Mitochondrial Proteins*/metabolism ; Mitochondrial Proteins*/genetics ; Mitophagy*; Mitochondria/metabolism ; Animals ; Mice ; Mice, Knockout ; Autophagy ; Male ; Mice, Inbred C57BL |
| Abstract: | Aging is associated with mitochondrial dysfunction and altered autophagic processes, particularly in secretory organs such as the salivary glands. In this study, we investigated metabolic changes and their interactions with mitophagy in primary salivary gland cells (PSGCs) from klotho-deficient (kl-/-) mice, a model of accelerated aging. We observed a significant reduction in both mitochondrial number and mitochondrial DNA copy number in the PSGCs of kl-/- mice compared with those of wild-type (WT) controls. In contrast, lysosomal abundance was markedly increased in PSGCs from kl-/- mice. Moreover, the expression of the autophagy marker LC3B was significantly upregulated in kl-/- PSGCs, and the expression of the mitophagy markers BNIP3 and NIX increased. Our metabolomic profiling revealed disrupted spermidine biosynthesis in the salivary glands of kl-/- mice. Interestingly, spermidine treatment in kl-/- PSGCs increased the number of mitochondria and suppressed mitophagy, as indicated by the reduced expression of BNIP3 and LC3B. Conversely, in WT PSGCs, spermidine induced the expression of autophagy and mitophagy markers, namely, BNIP3 and LC3B. These findings suggest that accelerated aging in mice impairs mitochondrial homeostasis and alters autophagy/mitophagy pathways in salivary gland cells, potentially through the dysregulation of spermidine metabolism. Our results provide insight into the molecular mechanisms of aging in salivary glands and reveal the potential role of polyamine metabolism in maintaining mitophagy during aging.; (Copyright © 2024. Published by Elsevier B.V.) |
| Competing Interests: | Declaration of competing interest The authors declare no competing interests. |
| Contributed Indexing: | Keywords: Aging; Mitochondria; Mitophagy; Salivary glands; Spermidine |
| Substance Nomenclature: | U87FK77H25 (Spermidine); 0 (Map1lc3b protein, mouse); 0 (BNip3 protein, mouse); 0 (Microtubule-Associated Proteins); 0 (Membrane Proteins); 0 (Mitochondrial Proteins) |
| Entry Date(s): | Date Created: 20251218 Date Completed: 20260108 Latest Revision: 20260108 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.bbagen.2025.130897 |
| PMID: | 41412391 |
| Database: | MEDLINE |
Journal Article