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Freddy Benning

@fmcbenning.bsky.social

135 followers 279 following 15 posts

Mitochondria | structural biology | molecular assemblies | eukaryogenesis

Freddy Benning @fmcbenning.bsky.social · 23/06/2025

7/🔬 Using TEM, cryo-ET and fluorescence microscopy, we describe a phenotype that is specific to a mutant of these four ASR-identified residues, which features box-like shaped cristae and longer average cristae lengths.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

6/🔬 Several TEM studies have shown that Mic60 and Mitofilin deletions result in detached cristae. We observe the same phenotype for our knockout variants. ✅ 🤯 Surprisingly, Mitofilin ancestors which rescue respiratory growth like wildtype have knockout-like detached cristae.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

5/🎯 Comparing reconstructed ancestors, we identified four residues in the Mitofilin domain that are sufficient for rescuing respiration.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

4/🧫 We found that common Mitofilin ancestors as far back as the putative last opisthokont common ancestor #LOCA rescues respiration in yeast. ✅

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

3/❓How did Mitofilin-supported respiration diverge between yeast 🍺 and humans 👤? 💻🦖🧪 We used ancestral sequence reconstruction #ASR to reconstruct ancestral Mitofilin sequences and resurrected them for in vivo characterization.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

2/ 🧫 Using respiratory growth assays, we found that swapping the yeast Mitofilin domain with that of another yeast rescued respiration. ✅ Replacing it with human or bacterial homologues at the endogenous locus did not rescue respiration. 💀 ❗This is in contrast to previous plasmid-based work.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

1/ ❓Mic60, a core component of the #MICOS complex in the #mitochondrial inner membrane, is crucial for the organization of #cristae and their functions. It's unclear, how Mic60's #Mitofilin domain encodes cristae-supported functions like cellular respiration.

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