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ITraq proteomics of SARM1-OE/HEK293 cells

ABSTRACT: SARM1 (sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1) is an inducible NAD-consuming enzyme that drives axon degeneration and a form of non-apoptotic cell death termed sarmoptosis. Using SARM1-overexpressing HEK293 cells, we previously showed that the cell-permeant NMN mimetic CZ-48 activates SARM1, depletes cellular NAD and ATP, and induces regulated, propidium iodide (PI)-positive, non-apoptotic cell death that is potently suppressed by the HSP70-family ATP-competitive inhibitor VER-155008 (VER). To investigate the proteome-wide changes underlying CZ-48-induced SARM1 activation and VER-mediated rescue, we performed iTRAQ-based quantitative proteomics on SARM1-overexpressing HEK293 cells treated with vehicle control, 20 μM VER alone, 100 μM CZ-48 alone, or CZ-48 plus VER for 16 h, with biological replicates per group. This dataset was used to identify CZ-48-responsive proteins whose abundance changes were reversed by VER co-treatment, focusing on HSP70/chaperone-related proteostasis proteins, mitochondrial and metabolic proteins, and cell-death-related proteins, in order to elucidate mechanisms of SARM1-driven ATP collapse and mitochondrial dysfunction during sarmoptosis.

ORGANISM(S): Homo Sapiens

SUBMITTER: Lei Fang

PROVIDER: PXD082054 | iProX | Sat Aug 01 00:00:00 GMT+01:00 2026

REPOSITORIES: iProX

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