Protein quality control articles from across Nature Portfolio

The Lon protease is an important protein degradation machine and is conserved across the three domains of life. Here, the authors describe a small proteotoxic stress-induced protein that functions as an allosteric activator of Lon.

A complex interplay of various backgrounds and conditions determines the body fat levels of individuals. Here, the authors identify HSP47 as a pivotal determinant of body adiposity which is abundantly expressed in fat tissue and influenced by factors such as diet, exercise, hormones, and genetics.

N-terminal acetylation is a common modification with unclear function. Here, using multidimensional proteomics, the authors found that NatA-deficient yeast show increased ribosomal protein degradation and decreased ribosome thermostability, suggesting that N-terminal acetylation enhances proteome stability.

Many age-related disorders, such as neurodegenerative diseases, are associated with protein misfolding. Here, the authors identify LONRF2 as a protein quality control ubiquitin ligase that is expressed in neurons and ubiquitylates misfolded TDP-43 and hnRNP M1 and show that loss of Lonrf2 in mice results in late-onset motor neuron degeneration, whereas its ectopic expression partially rescued the phenotypes observed in motor neurons derived from patients with amyotrophic lateral sclerosis.

The accumulation of cytotoxic deoxysphingolipids causes retinopathies through unknown mechanisms. Here the authors use retinal organoids to show that photoreceptor toxicity is mediated by unfolded protein response signaling.

Perez-Bermejo et al. performed an in-depth study on a variant in the BAG3 gene that has been previously associated with lowered incidence of heart failure and show that, in induced pluripotent stem cell-derived cardiomyocytes engineered to express such BAG3 variant, the interactome of the corresponding BAG3 protein has changed, rendering the engineered cardiomyocytes more resistant to a well-known cardiotoxic drug.

Mitochondrial-derived vesicles (MDVs) transfer mitochondrial content to lysosomes and peroxisomes. A study now reveals that MDVs deliver β-barrel proteins and fully assembled mitochondrial complexes for lysosomal degradation, establishing an important role for MDVs in mitochondrial protein quality control.