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Updated: Mar 29, 2026

Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
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Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications

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MFN2-PERK Axis Regulates ER Stress in Parotid Glands of Aged Mice via MAMs

Y Chen1,2, Y M Xu3,4, L L Zhu1,2

  • 1Changsha Stomatological Hospital, Changsha, Hunan, China.

Journal of Dental Research
|March 28, 2026
PubMed

Insights

Aging impairs parotid gland function by disrupting mitochondria-associated membranes (MAMs) and endoplasmic reticulum (ER) stress via the MFN2-PERK pathway. Treatments targeting this axis may restore gland function.

Area of Science:

  • Cell Biology
  • Aging Research
  • Glandular Physiology

Background:

  • Parotid gland morphology and function decline with age, but the underlying mechanisms remain unclear.
  • Mitochondria-associated membranes (MAMs), crucial for ER-mitochondria communication, are compromised during aging.
  • Endoplasmic reticulum (ER) stress, mediated by Protein kinase R-like endoplasmic reticulum kinase (PERK) signaling, is implicated in age-related cellular dysfunction.

Purpose of the Study:

  • To investigate the impact of aging on MAMs integrity and ER stress in mouse parotid glands.
  • To elucidate the role of MFN2 and its interaction with PERK in age-related parotid gland dysfunction.
  • To evaluate the therapeutic potential of targeting the MFN2-PERK axis.

Main Methods:

  • Comparative analysis of parotid gland morphology and MAMs integrity in aged versus young mice.
  • Assessment of ER stress markers, including PERK pathway activation.
  • Evaluation of MFN2 expression and its interaction with PERK.
  • Pharmacological intervention using 4-phenylbutyric acid (4-PBA) and GSK2606414 (PERK antagonist).

Main Results:

  • Aged mice exhibited parotid gland and mitochondrial abnormalities, with reduced MAMs integrity.
  • PERK signaling was activated in aged parotid glands, correlating with MFN2 downregulation and disrupted mitochondrial dynamics.
  • Aging impaired MAMs function by inhibiting the MFN2-PERK interaction.
  • 4-PBA and GSK2606414 treatments improved MAMs integrity, reduced ER stress, and decreased apoptosis.

Conclusions:

  • Disruption of the MFN2-PERK axis-mediated ER-mitochondrion connection is a key factor in aging-induced parotid gland dysfunction.
  • Targeting ER stress and MAMs integrity holds therapeutic promise for age-related salivary gland dysfunction.
Keywords:
agingendoplasmic reticulum stressmitochondria-associated membranesmitofusin 2oxidative stressprotein kinase R-like endoplasmic reticulum kinase

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