Key result
TRIM16 protects cells from oxidative and proteotoxic stress by activating NRF2 and mediating aggrephagy to safely dispose of misfolded proteins.
Why the study?
Understanding the molecular mechanisms regulating protein aggregate turnover may enable therapeutic interventions for proteinopathies.
Understanding TRIM16's role in protein aggregate turnover provides potential therapeutic targets for proteinopathies.
Protein quality control mechanisms need cardiac validation; leaves open chaperone-targeted therapies in cardiomyopathy.
The cellular stresses, genetic mutations, and environmental factors can critically affect the protein quality control checkpoints resulting in protein misfolding. Molecular chaperones play a crucial role in maintaining the healthy proteome by refolding the misfolded proteins into the native functional conformations. However, if they fail to refold the misfolded proteins into the native state, they are targeted by proteolytic systems for degradation. If the misfolded protein numbers increase more than what a cell can resolve, they get converted protein aggregates/inclusion bodies. The inclusion bodies are less cytotoxic than misfolded proteins. The enhanced production of misfolded proteins and protein aggregates are linked to several diseases collectively termed proteinopathies, which includes several neurodegenerative disorders. The understanding of molecular mechanisms that regulate the turnover of protein aggregates will pave path for therapeutic interventions of proteinopathies. In a recent report, we showed that a tripartite motif (TRIM) family protein, TRIM16 streamlines the process of protein aggregates turnover by regulating the NRF2-p62 axis and autophagy.
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Jena et al. (2018) conducted a review in Proteinopathies and Cancer. TRIM16 knockout vs. Wild-type was evaluated. TRIM16 protects cells from oxidative and proteotoxic stress by activating NRF2 and mediating aggrephagy to safely dispose of misfolded proteins.
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