Skip to main content
ARS Home » Northeast Area » Leetown, West Virginia » Cool and Cold Water Aquaculture Research » Research » Publications at this Location » Publication #407477
Research Project: Integrated Research Approaches for Improving Production Efficiency in Rainbow Trout

Location: Cool and Cold Water Aquaculture Research

Title: Chaperone-mediated autophagy in fish: A key function amid a changing environment

Author
item SCHNEBERT, SIMON - Inrae
item VELEZ, EMILIO - Inrae
item MAXIME, GOGUET - Inrae
item KARINE, DIAS - Inrae
item VERON, VINCENT - Inrae
item GARCÍA-PÉREZ, ISABEL - Inrae
item FONTAGNÉ-DICHARRY, STEPHANIE - Inrae
item BERNARD, AMELIE - Laboratory Of Membrane Biology (LBM)
item BEAUMATIN, FLORIAN - Inrae
item HERPIN, AMAURY - Inrae
item Radler, Lisa
item Cleveland, Beth
item SEILIEZ, IBAN - Inrae

Submitted to: Autophagy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/10/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: In mammals, chaparone-mediated autophagy (CMA) has been characterized as a cellular mechanism important for regulating nutrient metabolism and stress response. However, existence of the CMA mechanism has not been clearly established in fish. In this study we determine that genetic components of CMA machinery are ubiquitously expressed in rainbow trout tissues and provide evidence for CMA activity in liver tissue. Additionally, we use gene editing techniques to disrupt CMA activity in rainbow trout; mutants exhibited improved growth and altered nutrient metabolism. These findings characterize the significance of CMA as a metabolic regulator of growth and nutrient partitioning in rainbow trout, indicating that feeding strategies that specifically regulate CMA activity may be beneficial for improving production efficiency.

Technical Abstract: Chaperone-mediated Autophagy (CMA) is a prominent lysosomal-dependent pathway responsible for protein degradation, maintaining cellular proteostasis in the face of various stressors like starvation, oxidative stress, and hypoxia. While extensively studied in mammals, CMA's existence in fish has only been confirmed recently, offering exciting insights into its role in species facing environmental stress. In this study, we first show that CMA-related factors are ubiquitously expressed during early development as well as in several adult tissues of rainbow trout (RT, Oncorhynchus mykiss), a species of both economic and ecological importance. In order to firmly establish the existence of functional CMA activity in this species, we then performed an in vitro CMA activity assay using isolated lysosomes. Our results show that RT undoubtedly exhibits CMA activity, which increases 21-fold during nutrient deprivation, a known CMA inducer. Finally, we used the CRISPR-Cas9 genome editing tool to generate a knock-out (KO) line lacking a key CMA rate-limiting protein, the lysosome-associated membrane protein 2A (Lamp2A). Lamp2A KO fish showed significant physiological alterations, including enhanced body size and altered organ indices, as well as substantial remodeling of the liver proteome. Furthermore, we propose the use of the CMA activation score as a potential biomarker for assessing fish homeostasis, given its demonstrated involvement in stress response. Altogether, our data shows that in addition to being present in RT, CMA shapes a distinct part of the proteome related to major metabolic pathways, emphasizing its crucial role in evaluating the impact of environmental threats on fish.