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CMA restricted to mammals and birds: myth or reality?

Chaperone-mediated autophagy (CMA) most likely appeared much earlier during evolution than initially thought. These results shed an entirely new light on the evolution of CMA.

Lamp2A in fish © in Lescat et al., 2018
Updated on 03/12/2019
Published on 03/01/2019

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.

Reference

Lescat L, Herpin A, Mourot B, Véron V, Guiguen Y, Bobe J, Seiliez I. CMA restricted to mammals and birds: myth or reality? Autophagy. 2018;14(7):1267-1270. doi: 10.1080/15548627.2018.1460021