In a recent work, @buzzbaum.bsky.social and colleagues showed an Asgard archaeon with internal vesicles. www.biorxiv.org/content/10.1... How might Asgard ESCRT-III have contributed to compartmentalization?

Through membrane fission! We show in vitro that the Asgard Heimdallarchaeota (Heimdall) ESCRT-IIIA subunit is inherently capable of triggering fission upon subunit turnover driven by ATP hydrolysis by Vps4. And the key question: what actually destabilizes the membrane when ESCRT-IIIA turns over?

Meet Hofund, the N-terminal amphipathic helix of 15 aa in Heimdall ESCRT-IIIA (named after Heimdall’s sword). How do we know Hofund is the molecular trigger for fission? Remove Hofund → ESCRT-IIIA loses fission activity. Add Hofund alone → uncontrolled fission.

Is this Asgard-specific, or conserved with their eukaryotic paralogs? Hard to tell, since the exact molecular mechanism of fission by eukaryotic ESCRT-III remains blurry, probably due to its complexity. Let’s figure it out!

Eukaryotic ESCRT-IIIA paralogs, known to form heteropolymers, retain Hofund elements at their N-termini. In yeast, mutating these elements blocks ESCRT-III-dependent Mup1 transport to vacuoles. So these elements matter in eukaryotes too.

The crucial test: We fused Heimdall Hofund to a fission-defective yeast ESCRT-III protein (Did2). This chimera restored Mup1 trafficking to vacuoles back to wt! A short amphipathic helix, present in Asgard and retained as fragments in eukaryotes, acts as a minimal membrane fission trigger!

All credits to the dreamteam that made this possible! what a pleasure and honor working with these people! 🥰 @diorgeps.bsky.social @mhakala.bsky.social @juanmagararc.bsky.social @joshuatran.bsky.social @mudgal17.bsky.social @Carlos Marcuello @Andrea Merino