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Updated: Jan 28, 2026

Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration
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Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration

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PHB2 mitigates intervertebral disc degeneration by modulating mitophagy to inhibit necroptosis in nucleus pulposus

Zhenyu Zhu1, Yongcheng Liang2, Xiaowen Liu1

  • 1Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University, Shanghai 200003, P.R. China.

Iscience
|January 26, 2026
PubMed

Insights

Mitophagy disruption contributes to cell death in intervertebral disc degeneration. Activating mitophagy, particularly via the protein PHB2, protects against cell death and preserves disc structure.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Orthopedics

Background:

  • Intervertebral disc degeneration (IVDD) involves nucleus pulposus (NP) cell loss due to inflammatory and mitochondrial stress pathways.
  • Mitophagy, a key mitochondrial quality control process, is implicated in cell fate during degeneration.

Purpose of the Study:

  • To investigate the role of mitochondrial quality control, specifically mitophagy, in regulating necroptosis during IVDD.
  • To identify key molecular regulators linking mitophagy to necroptosis suppression in NP cells.

Main Methods:

  • Utilized human tissues, mouse and rat models of IVDD, and human NP cells treated with necroptosis inducers (TNF-α, SM-164, Z-VAD-FMK).
  • Assessed mitochondrial damage, mitophagy levels, and necroptotic signaling.
  • Investigated the role of mitochondrial protein PHB2 in regulating mitophagy and necroptosis.

Main Results:

  • Necroptotic cells showed mitochondrial damage and reduced mitophagy; mitophagy activation inhibited necroptosis and preserved extracellular matrix.
  • PHB2 was identified as a crucial regulator; PHB2 loss impaired mitophagy and exacerbated necroptosis, while PHB2 overexpression restored mitophagy and reduced degeneration.
  • In vivo PHB2 delivery protected disc structure by mitigating necroptosis.

Conclusions:

  • Mitophagy is a critical protective mechanism against necroptosis in IVDD.
  • PHB2 acts as a key mitochondrial regulator, linking mitophagy to necroptosis suppression.
  • Targeting PHB2-mediated mitophagy offers a potential therapeutic strategy for IVDD.
Keywords:
Biological sciencesCell biologyHealth sciencesMolecular biology

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