Experimental cell researchOct 13, 2026

Mechanical support from OPTN-TRIP6 and actin helps close cell structures needed for face and skull development

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 14, 2026

Abstract

Absence of Optn in zebrafish and mouse models leads to systemic bone loss and craniofacial abnormalities.

Optineurin (OPTN) is involved in the process of bone development by promoting the mineralization of matrix through orofacial mesenchymal stem cells.
OPTN mediates the release of amorphous calcium phosphate by initiating mitophagy through a process known as liquid-liquid phase separation.
In the absence of OPTN, there is a significant accumulation of dysfunctional mitochondria due to impaired mitophagy.
OPTN recruits TRIP6 to damaged mitochondria, which is essential for the polymerization of actin filaments and the remodeling of the cytoskeleton.
The OPTN-TRIP6-F-actin interaction is crucial for the closure of autophagosomes, maintaining mitochondrial health and supporting craniofacial bone formation.

Simplified

The development of craniofacial bones is highly dependent on the intramembranous ossification process driven by orofacial mesenchymal stem cells (OMSCs). Optineurin (OPTN), a traditional mitophagy receptor, promotes OMSC matrix mineralization by mediating the extracellular release of amorphous calcium phosphate (ACP) through the initiation of mitophagy via liquid-liquid phase separation. However, the dynamic mechanisms by which OPTN regulates mitochondrial engulfment remain elusive. In this work, we show that in both zebrafish and mouse models, Optn absence causes systemic bone loss and craniofacial abnormalities. Mechanistically, OPTN recruits thyroid receptor-interacting protein 6 (TRIP6) to the surface of damaged mitochondria, inducing local F-actin polymerization and remodeling, which relies on cytoskeletal mechanical forces to support the bending and closure of the phagophore. The depletion of OPTN or TRIP6 significantly impairs mitophagy flux, triggering a massive accumulation of dysfunctional mitochondria. Overall, this study elucidates that the OPTN-TRIP6-F-actin axis ensures autophagosome closure through cytoskeletal remodeling, revealing a novel paradigm in which cytoskeletal mechanical regulation maintains mitochondrial homeostasis to orchestrate craniofacial osteogenesis.

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Mechanical support from OPTN-TRIP6 and actin helps close cell structures needed for face and skull development

Abstract

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