The role of Oxr1-mediated autophagy in regulating mitochondrial homeostasis and osteoclastogenesis

Xiaojun Chen

doi:10.26182/jx43-vr48

The role of Oxr1-mediated autophagy in regulating mitochondrial homeostasis and osteoclastogenesis

Xiaojun Chen

School of Molecular Sciences

Research output: Thesis › Doctoral Thesis

47 Downloads (Pure)

Abstract

Osteoclasts (OCs) are rich in mitochondria, relying heavily on oxidative phosphorylation for differentiation and maturation. Their excessive activity drives bone disorders. RANKL signaling promotes oxidative phosphorylation (OXPHOS), generating significant reactive oxygen species(ROS). Autophagy removes damaged mitochondria to maintain cellular homeostasis. We determinedOxr1 is a key regulator. Oxr1 deficiency impaired osteoclast differentiation and function, increasing ROS and causing mitochondrial defects due to the impaired autophagic degradation flux. OXR1binds directly to KEAP1, facilitating mitochondrial ubiquitination and subsequent autophagic clearance of damaged mitochondria. Targeting Oxr1 could be a promising therapeutic strategy for bone diseases.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Swaminatha Iyer, Iyer, Supervisor Jiang, Haibo, Supervisor Chen, Kai, Supervisor
Award date	12 Jun 2026
DOIs	https://doi.org/10.26182/jx43-vr48
Publication status	Unpublished - 2026

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10.26182/jx43-vr48

THESIS - DOCTOR OF PHILOSOPHY - CHEN Xiaojun – 2026
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UWA Dean’s list
Chen, X. (Recipient), 2026
Prize: Award

2 Article

β-Sitosterol inhibits osteoclast activity and reduces ovariectomy-induced bone loss by regulating the cAMP and NF-κB signaling pathways
Guo, H., Chen, X., Li, J., Mo, G., Li, Y., Tang, Y., Kai, Y. & Zhang, S., Jun 2025, In: Cellular Signalling. 130, p. 1-13 13 p., 111672.
Research output: Contribution to journal › Article › peer-review
6 Link opens in a new tab Citations (Scopus)
The therapeutic effect of Fufang Zhenshu Tiaozhi (FTZ) on osteoclastogenesis and ovariectomized-induced bone loss: evidence from network pharmacology, molecular docking and experimental validation
Chen, X., Wang, J., Tang, L., Ye, Q., Dong, Q., Li, Z., Hu, L., Ma, C., Xu, J. & Sun, P., 12 Jul 2022, In: Aging. 14, 14, p. 5727-5748 22 p.
Research output: Contribution to journal › Article › peer-review

Open Access
19 Link opens in a new tab Citations (Scopus)

Cite this

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title = "The role of Oxr1-mediated autophagy in regulating mitochondrial homeostasis and osteoclastogenesis",

abstract = "Osteoclasts (OCs) are rich in mitochondria, relying heavily on oxidative phosphorylation for differentiation and maturation. Their excessive activity drives bone disorders. RANKL signaling promotes oxidative phosphorylation (OXPHOS), generating significant reactive oxygen species(ROS). Autophagy removes damaged mitochondria to maintain cellular homeostasis. We determinedOxr1 is a key regulator. Oxr1 deficiency impaired osteoclast differentiation and function, increasing ROS and causing mitochondrial defects due to the impaired autophagic degradation flux. OXR1binds directly to KEAP1, facilitating mitochondrial ubiquitination and subsequent autophagic clearance of damaged mitochondria. Targeting Oxr1 could be a promising therapeutic strategy for bone diseases.",

keywords = "OXR1, Osteoclasts, Mitochondrial homeostasis, Autophagy, KEAP1",

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doi = "10.26182/jx43-vr48",

language = "English",

school = "The University of Western Australia",

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AU - Chen, Xiaojun

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N2 - Osteoclasts (OCs) are rich in mitochondria, relying heavily on oxidative phosphorylation for differentiation and maturation. Their excessive activity drives bone disorders. RANKL signaling promotes oxidative phosphorylation (OXPHOS), generating significant reactive oxygen species(ROS). Autophagy removes damaged mitochondria to maintain cellular homeostasis. We determinedOxr1 is a key regulator. Oxr1 deficiency impaired osteoclast differentiation and function, increasing ROS and causing mitochondrial defects due to the impaired autophagic degradation flux. OXR1binds directly to KEAP1, facilitating mitochondrial ubiquitination and subsequent autophagic clearance of damaged mitochondria. Targeting Oxr1 could be a promising therapeutic strategy for bone diseases.

AB - Osteoclasts (OCs) are rich in mitochondria, relying heavily on oxidative phosphorylation for differentiation and maturation. Their excessive activity drives bone disorders. RANKL signaling promotes oxidative phosphorylation (OXPHOS), generating significant reactive oxygen species(ROS). Autophagy removes damaged mitochondria to maintain cellular homeostasis. We determinedOxr1 is a key regulator. Oxr1 deficiency impaired osteoclast differentiation and function, increasing ROS and causing mitochondrial defects due to the impaired autophagic degradation flux. OXR1binds directly to KEAP1, facilitating mitochondrial ubiquitination and subsequent autophagic clearance of damaged mitochondria. Targeting Oxr1 could be a promising therapeutic strategy for bone diseases.

KW - OXR1

KW - Osteoclasts

KW - Mitochondrial homeostasis

KW - Autophagy

KW - KEAP1

U2 - 10.26182/jx43-vr48

DO - 10.26182/jx43-vr48

M3 - Doctoral Thesis

ER -

The role of Oxr1-mediated autophagy in regulating mitochondrial homeostasis and osteoclastogenesis

Abstract

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Prizes

UWA Dean’s list

Research output

β-Sitosterol inhibits osteoclast activity and reduces ovariectomy-induced bone loss by regulating the cAMP and NF-κB signaling pathways

The therapeutic effect of Fufang Zhenshu Tiaozhi (FTZ) on osteoclastogenesis and ovariectomized-induced bone loss: evidence from network pharmacology, molecular docking and experimental validation

Cite this