Role of mitochondrial dysfunction in the pathogenesis of rheumatoid arthritis: Looking closely at fibroblast- like synoviocytes

Promila, Lakra; Joshi, Anubha; Khan, Shazia; Aggarwal, Amita; Lahiri, Amit

doi:10.1016/j.mito.2023.10.004

Mitochondrion

2023

DOI: 10.1016/j.mito.2023.10.004

|View full text |Cite

Role of mitochondrial dysfunction in the pathogenesis of rheumatoid arthritis: Looking closely at fibroblast- like synoviocytes

Lakra Promila,

Anubha Joshi,

Shazia Khan

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Preprint1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Mitochondrial calcium uniporter regulates human fibroblast-like synoviocytes invasion via altering mitochondrial dynamics and dictates rheumatoid arthritis pathogenesis

Promila,

Sarkar,

Guleria

et al. 2024

Preprint

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is characterized by the aggressive migration and invasion of fibroblast-like synoviocytes (FLS) into cartilage and bone, a process that is significantly influenced by mitochondrial calcium uptake. This study highlights the critical role of mitochondrial calcium uniporter (MCU) in regulating FLS migration and mitochondrial dynamics, and its potential as a therapeutic target in RA. Notably, RA-FLS exhibited increased MCU expression and mitochondrial dysfunction compared to controls. Treatment with Ru360, a potent MCU inhibitor significantly reduced RA-FLS migration, calcium influx, and mitochondrial reactive oxygen species (ROS) levels, while restoring mitochondrial morphology and enhancing ATP production. Further analysis of MCU complex expression revealed elevated levels of MCU and other regulatory subunits (EMRE, MICU1, MICU2) in RA-FLS compared to controls, indicating mitochondrial dysfunction in RA. Mechanistically, MCU inhibition altered gene expression related to cytoskeletal dynamics, focal adhesion, and metabolic pathways. In human RA-FLS, MCU inhibition suppressed migration and invasion both in vitro and in vivo. The interaction between MCU and Miro1, essential for mitochondrial transport, was validated, and its disruption impaired FLS migration. Our findings highlight MCU as a promising therapeutic target to inhibit FLS migration and ameliorate RA progression.

show abstract

Mitochondrial calcium uniporter regulates human fibroblast-like synoviocytes invasion via altering mitochondrial dynamics and dictates rheumatoid arthritis pathogenesis

Promila,

Sarkar,

Guleria

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Role of mitochondrial dysfunction in the pathogenesis of rheumatoid arthritis: Looking closely at fibroblast- like synoviocytes

Cited by 1 publication

References 108 publications

Mitochondrial calcium uniporter regulates human fibroblast-like synoviocytes invasion via altering mitochondrial dynamics and dictates rheumatoid arthritis pathogenesis

Mitochondrial calcium uniporter regulates human fibroblast-like synoviocytes invasion via altering mitochondrial dynamics and dictates rheumatoid arthritis pathogenesis

Contact Info

Product

Resources

About