Mitochondrial ROS and Mitophagy in Intervertebral Disc Degeneration: Mechanistic Interplay and Links to Regulated Cell Death
- 1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Abstract
Intervertebral disc degeneration (IVDD) develops through interacting mechanical, matrix, nutritional, inflammatory and age-related processes. Mitochondrial reactive oxygen species (mtROS) and mitophagy participate in some of these contexts, but current evidence does not place mitophagy failure at the start of every degenerative trajectory. Most mechanistic studies have been performed in nucleus pulposus (NP) cells. In these models, mechanical overload, inflammatory mediators and oxidant stress can depolarize mitochondria, disturb fission–fusion balance and increase mtROS. Mitophagy can limit injury when damaged cargo is selected and delivered through a competent lysosomal pathway; accumulation of pathway markers during blocked flux, or mitochondrial clearance that is not matched by renewal, need not be protective. The most extensive mechanistic literature concerns apoptosis and senescence. Evidence linking mitochondrial quality control to pyroptosis and ferroptosis is growing but remains model-dependent, whereas direct evidence for necroptosis is comparatively sparse. We use a capacity-matching framework to organize these findings around damage burden, cargo selection, lysosomal completion and mitochondrial renewal within the regional metabolic constraints of the disc. This is an interpretive framework rather than a newly identified pathway. Its purpose is to define testable conditions under which mitophagy is likely to be protective, insufficient or maladaptive, while preserving the distinction between NP-derived evidence and the more limited evidence from annulus fibrosus and cartilage endplate cells.
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BibTeX
@article{wang2026mitochondrial,
title = {{Mitochondrial ROS and Mitophagy in Intervertebral Disc Degeneration: Mechanistic Interplay and Links to Regulated Cell Death}},
author = {Lice Wang and Kai Cao and Haozhe Cheng and Zhong Fang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219628},
url = {https://www.mdpi.com/1422-0067/27/21/9628},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mitochondrial ROS and Mitophagy in Intervertebral Disc Degeneration: Mechanistic Interplay and Links to Regulated Cell Death
AU - Lice Wang
AU - Kai Cao
AU - Haozhe Cheng
AU - Zhong Fang
PY - 2026
DA - 2026/10/28
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219628
UR - https://www.mdpi.com/1422-0067/27/21/9628
AB - Intervertebral disc degeneration (IVDD) develops through interacting mechanical, matrix, nutritional, inflammatory and age-related processes. Mitochondrial reactive oxygen species (mtROS) and mitophagy participate in some of these contexts, but current evidence does not place mitophagy failure at the start of every degenerative trajectory. Most mechanistic studies have been performed in nucleus pulposus (NP) cells. In these models, mechanical overload, inflammatory mediators and oxidant stress can depolarize mitochondria, disturb fission–fusion balance and increase mtROS. Mitophagy can limit injury when damaged cargo is selected and delivered through a competent lysosomal pathway; accumulation of pathway markers during blocked flux, or mitochondrial clearance that is not matched by renewal, need not be protective. The most extensive mechanistic literature concerns apoptosis and senescence. Evidence linking mitochondrial quality control to pyroptosis and ferroptosis is growing but remains model-dependent, whereas direct evidence for necroptosis is comparatively sparse. We use a capacity-matching framework to organize these findings around damage burden, cargo selection, lysosomal completion and mitochondrial renewal within the regional metabolic constraints of the disc. This is an interpretive framework rather than a newly identified pathway. Its purpose is to define testable conditions under which mitophagy is likely to be protective, insufficient or maladaptive, while preserving the distinction between NP-derived evidence and the more limited evidence from annulus fibrosus and cartilage endplate cells.
SN - 1422-0067
ER -