Modulation of protease expression by the transcription factor Ptx1/PITX regulates protein quality control during aging

• DOI: 10.1016/j.celrep.2022.111970
• Publication Date: 2023-01-10T10:52:07Z
• Authors: Jianqin Jiao; Michelle Curley; Flavia A. Graca; Maricela Robles-M...; Abbas Shirinifard; David Finkelstein; Beisi Xu; Yiping Fan; Fabio Demontis
• Keywords: Proteostasis; TFEB; Deubiquitinating enzyme

Protein quality control is important for healthy aging and dysregulated in age-related diseases. The autophagy-lysosome ubiquitin-proteasome are key proteostasis, but it remains largely unknown whether other proteolytic systems also contribute to maintain proteostasis during aging. Here, we find that expression of enzymes (proteases/peptidases) distinct from the declines skeletal muscle Drosophila. Age-dependent protease downregulation undermines as demonstrated by increase detergent-insoluble poly-ubiquitinated proteins pathogenic huntingtin-polyQ levels response knockdown. Computational analyses identify transcription factor Ptx1 (homologous human PITX1/2/3) a regulator expression. Consistent with this model, protein aging, RNAi counteracts age-associated Moreover, improves protease-dependent manner extends lifespan. These findings indicate proteases their transcriptional modulator ensure