LIPT1 is associated with rheumatoid arthritis fibroblast phenotypes and Wnt-related signaling

Lipoyltransferase 1 (LIPT1) supports mitochondrial protein lipoylation, but its role in rheumatoid arthritis (RA) fibroblasts remains unclear. We integrated synovial transcriptomes from 39 RA and 27 control samples, evaluated expression in an independent cohort of 152 RA and 28 healthy synovial samples, and examined peripheral blood mononuclear cells from six RA participants and six healthy controls. Commercially obtained primary RA fibroblast-like synoviocytes (RA-FLS) underwent LIPT1 silencing and treatment with the Wnt/β-catenin agonist SKL2001. Independent synovial validation showed higher LIPT1, but not metal-regulatory transcription factor 1, expression in RA. LIPT1 depletion reduced migration and Cell Counting Kit-8 signals, increased apoptosis-associated Annexin V positivity and intracellular copper, increased superoxide dismutase and peroxidase activities, and decreased malondialdehyde. WNT5A transcripts, WNT5A/B-reactive protein signals, and total β-catenin expression also decreased. Compared with knockdown alone, SKL2001 increased migration, Cell Counting Kit-8 signals, malondialdehyde, and LIPT1 and Wnt-related expression while reducing Annexin V positivity, copper content, and antioxidant enzyme activities. These findings associate LIPT1 with RA-FLS survival and migration. SKL2001 counteracts the effects of LIPT1 depletion, although the underlying signaling mechanism remains unresolved.