CMA restricted to mammals and birds: myth or reality?

ABSTRACT

Chaperone-mediated autophagy (CMA) is a major pathway of lysosomal proteolysis essential for the control of intermediary metabolism. So far, the absence of any identifiable LAMP2A – a necessary and limiting protein for CMA – outside of the tetrapod clade, led to the paradigm that this cellular function was (presumably) restricted to mammals and birds. However, after we identified expressed sequences displaying high sequence homology with the mammalian LAMP2A in several fish species, our findings challenge that view and suggest that CMA likely appeared much earlier during evolution than initially thought. Hence, our results do not only shed an entirely new light on the evolution of CMA, but also bring new perspectives on the possible use of complementary genetic models, such as zebrafish or medaka for studying CMA function from a comparative angle/view.

KEYWORDS:

• Chaperone-mediated autophagy
• evolution
• fish
• LAMP2A
• RNA-seq

Acknowledgments

We thank AM Cuervo (Albert Einstein College of Medicine, NY) for helpful advice.

Competing financial interests

The authors declare no competing financial interests.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by the INRA ‘Animal Physiology and Livestock Systems’ Division, and the French National Research Agency (ANR-17-CE20-0033 ‘Fish-and-Chap’).