# Mitochondrial dysfunction in the bovine mammary gland: regulatory mechanisms and therapeutic strategies

**Authors:** Taiyu Shen, Ming Li, Xudong Sun, Zhaoju Deng, Hailey Pitts, Derek Nolan, Juan J. Loor, Chuang Xu

PMC · DOI: 10.1186/s40104-026-01361-7 · Journal of Animal Science and Biotechnology · 2026-03-18

## TL;DR

This review explores how mitochondrial dysfunction affects the bovine mammary gland and discusses possible treatments to reduce tissue damage and improve milk production.

## Contribution

The paper provides a comprehensive overview of mitochondrial regulatory mechanisms and therapeutic strategies specific to bovine mammary dysfunction.

## Key findings

- Mitochondrial homeostasis is essential for normal mammary gland function in cattle.
- Mitochondrial dysfunction contributes to mammary tissue damage and reduced milk yield.
- Targeted therapeutic strategies may help alleviate mitochondrial metabolic dysfunction in the mammary gland.

## Abstract

Periparturient metabolic stress or pathogen infections leading to inflammation reduce milk yield and cause mammary dysfunction, thus, causing severe economic losses to dairy farming. As the primary organelle for cellular energy production, calcium regulation, cell death, and metabolism, mitochondrial homeostasis plays a crucial role in maintaining normal mammary gland function. This review focuses on the regulatory mechanisms of mitochondrial homeostasis and the effect of mitochondrial dysfunction on homeostatic mechanisms in bovine mammary gland. Furthermore, we summarize several potential therapeutic strategies targeting mitochondrial metabolic dysfunction to alleviate mammary tissue damage.

## Full-text entities

- **Genes:** Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, TFAM (transcription factor A, mitochondrial) [NCBI Gene 510059], INS (insulin) [NCBI Gene 280829], PINK1 (PTEN induced kinase 1) [NCBI Gene 510683], GSK3A (glycogen synthase kinase 3 alpha) [NCBI Gene 536561], CCDC90B (coiled-coil domain containing 90B) [NCBI Gene 506046], TSC2 (TSC complex subunit 2) [NCBI Gene 504985], NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 497024] {aka NRF2}, MCUR1 (mitochondrial calcium uniporter regulator 1) [NCBI Gene 617129] {aka CCDC90A}, CGAS (cyclic GMP-AMP synthase) [NCBI Gene 782472] {aka MB21D1}, ATG5 (autophagy related 5) [NCBI Gene 532686], RARRES2 (retinoic acid receptor responder 2) [NCBI Gene 508990] {aka TIG2}, CREB3 (cAMP responsive element binding protein 3) [NCBI Gene 281715], DNMT1 (DNA methyltransferase 1) [NCBI Gene 281119] {aka DNMT}, TLR9 (toll like receptor 9) [NCBI Gene 282602], CASP1 (caspase 1) [NCBI Gene 514214], KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 532791], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 280828] {aka IL-8, IL8}, TOLLIP (toll interacting protein) [NCBI Gene 539480], ESRRA (estrogen related receptor alpha) [NCBI Gene 507834], PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 281993], MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 100139219], RHEB (Ras homolog, mTORC1 binding) [NCBI Gene 528204], NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 538639], PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 338446] {aka PPARGC-1A}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 281713] {aka CREB}, MIR148A (microRNA mir-148a) [NCBI Gene 790977] {aka MIRN148A, bta-mir-148a, mir-148a}, MUC (PAS-1 protein) [NCBI Gene 280870], TXN (thioredoxin) [NCBI Gene 280950], NRF1 (nuclear respiratory factor 1) [NCBI Gene 509232], SIRT1 (sirtuin 1) [NCBI Gene 613629], STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 533661] {aka STING, TMEM173}, cytochrome c [NCBI Gene 104968582], EIF4EBP2 (eukaryotic translation initiation factor 4E binding protein 2) [NCBI Gene 782397], OPA1 (OPA1 mitochondrial dynamin like GTPase) [NCBI Gene 524142], ATG101 (autophagy related 101) [NCBI Gene 513049] {aka C12orf44, C5H12orf44}, SENP1 (SUMO specific peptidase 1) [NCBI Gene 538091], TSC1 (TSC complex subunit 1) [NCBI Gene 533440], ULK2 (unc-51 like autophagy activating kinase 2) [NCBI Gene 618601], EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 509106], CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, TBK1 (TANK binding kinase 1) [NCBI Gene 533141], MFN2 (mitofusin 2) [NCBI Gene 534574], EIF4EBP1 (eukaryotic translation initiation factor 4E binding protein 1) [NCBI Gene 509613], CAT (catalase) [NCBI Gene 531682], BECN1 (beclin 1) [NCBI Gene 527278] {aka ATG6}, LOC101902760 (ubiquitin) [NCBI Gene 101902760], IRF7 (interferon regulatory factor 7) [NCBI Gene 100125591], TNF (tumor necrosis factor) [NCBI Gene 280943] {aka TNF-a, TNF-alpha, TNFa}, ULK1 (unc-51 like autophagy activating kinase 1) [NCBI Gene 526310], NFE2 (nuclear factor, erythroid 2) [NCBI Gene 514006], ACSS2 (acyl-CoA synthetase short chain family member 2) [NCBI Gene 506459], IL18 (interleukin 18) [NCBI Gene 281249], OPTN (optineurin) [NCBI Gene 534150], CALCOCO2 (calcium binding and coiled-coil domain 2) [NCBI Gene 281942] {aka NDP52}, ESR1 (estrogen receptor 1) [NCBI Gene 407238], TAX1BP1 (Tax1 binding protein 1) [NCBI Gene 535589], PYCARD (PYD and CARD domain containing) [NCBI Gene 282846] {aka ASC}, MFN1 (mitofusin 1) [NCBI Gene 515180] {aka MFN2}, FBXW7 (F-box and WD repeat domain containing 7) [NCBI Gene 540932]
- **Diseases:** EPEC (MESH:D004927), Bacterial infections (MESH:D001424), obesity (MESH:D009765), infections (MESH:D007239), diabetes (MESH:D003920), Mitochondrial dysfunction (MESH:D028361), Klebsiella pneumoniae (MESH:D007710), MAC-T (MESH:D001260), hypocalcemia (MESH:D006996), HS (MESH:D018882), hypoxia (MESH:D000860), MAMs (MESH:D015433), ketosis (MESH:D007662), tissue (MESH:D017695), dysfunction of the mammary gland (MESH:D005348), MECs (MESH:D009375), Metabolic disorders (MESH:D008659), mastitis (MESH:D008413), inflammation (MESH:D007249), infectious diseases (MESH:D003141), MCUR (MESH:D002128)
- **Chemicals:** fatty acid (MESH:D005227), rapamycin (MESH:D020123), tricarboxylic acid (MESH:D014233), Hesperidin (MESH:D006569), MDA (MESH:D008315), Folpet (MESH:C005020), AMP (MESH:D000249), Calcium (MESH:D002118), Curcumin (MESH:D003474), Ca2+ (-), BHB (MESH:D020155), carotenoid (MESH:D002338), lipid (MESH:D008055), pyridaben (MESH:C428725), c-di-AMP (MESH:C528998), ketone bodies (MESH:D007657), baicalin (MESH:C038044), resveratrol (MESH:D000077185), arginine (MESH:D001120), A-769662 (MESH:C512408), Puerarin (MESH:C033607), H2O2 (MESH:D006861), aflatoxin B1 (MESH:D016604), GTP (MESH:D006160), cGAMP (MESH:C584311), GSH (MESH:D005978), diterpenoid (MESH:D004224), ROS (MESH:D017382), NAD + (MESH:D009243), Lycopene (MESH:D000077276), lactose (MESH:D007785), FFA (MESH:D005230), hydroxybutyrate (MESH:D006885), glucose (MESH:D005947), c-di-GMP (MESH:C062025), Allicin (MESH:C006452), Quercetin (MESH:D011794), acetate (MESH:D000085), hydrocarbon (MESH:D006838), ammonia (MESH:D000641), flavonoid (MESH:D005419), Sulphur (MESH:D013455), LPS (MESH:D008070), polyphenol (MESH:D059808), ATP (MESH:D000255), CO2 (MESH:D002245), Tanshinone IIa (MESH:C021751)
- **Species:** Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Bos taurus (bovine, species) [taxon 9913], Curcuma longa (turmeric, species) [taxon 136217], Staphylococcus aureus (species) [taxon 1280], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Allium cepa (onion, species) [taxon 4679], Allium sativum (garlic, species) [taxon 4682], Scutellaria (genus) [taxon 4139], Salvia miltiorrhiza (Chinese salvia, species) [taxon 226208], Pueraria (genus) [taxon 3892], Escherichia coli (E. coli, species) [taxon 562]
- **Cell lines:** MAC-T — Bos taurus (Bovine), Transformed cell line (CVCL_U226), bMECs — Bos taurus (Bovine), Telomerase immortalized cell line (CVCL_B6BU)

## Full text

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## References

8 references — full list in the complete paper: https://tomesphere.com/paper/PMC12998065/full.md

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Source: https://tomesphere.com/paper/PMC12998065