Michelle Fry

1/ 🧵 Two classic mitochondrial pathways the TCA cycle and OXPHOS are taught as linked but distinct pathways. I’m happy to share our new work out in @cp-cell.bsky.social showing that in Acanthamoeba they're physically linked—with a TCA enzyme incorporated in ATP synthase. www.cell.com/cell/fulltex...

9/Thanks to the @hhmi-science.bsky.social Emerging Pathogens Initiative, @jcchildsfund.bsky.social , and Mark and Lisa Schwartz for funding our MitoTOL work.

1/ 🧵 Two classic mitochondrial pathways the TCA cycle and OXPHOS are taught as linked but distinct pathways. I’m happy to share our new work out in @cp-cell.bsky.social showing that in Acanthamoeba they're physically linked—with a TCA enzyme incorporated in ATP synthase. www.cell.com/cell/fulltex...

7/ This work shows what these inventories make possible. They let us ask not just which proteins are in mitochondria, but how conserved mitochondrial machines have been rewired, expanded, and repurposed across eukaryotic evolution?

1/ 🧵 Two classic mitochondrial pathways the TCA cycle and OXPHOS are taught as linked but distinct pathways. I’m happy to share our new work out in @cp-cell.bsky.social showing that in Acanthamoeba they're physically linked—with a TCA enzyme incorporated in ATP synthase. www.cell.com/cell/fulltex...

5/ This changes how we might think about metabolism and OXPHOS. They don’t have to be pathways connected only through shared cofactors and substrates. Mitochondria can organize enzymes into assemblies that could couple local metabolic chemistry to OXPHOS machinery.

1/ 🧵 Two classic mitochondrial pathways the TCA cycle and OXPHOS are taught as linked but distinct pathways. I’m happy to share our new work out in @cp-cell.bsky.social showing that in Acanthamoeba they're physically linked—with a TCA enzyme incorporated in ATP synthase. www.cell.com/cell/fulltex...

3/ The MDH dimer docks by wrapping an N-terminal extension around a small lineage-specific subunit we dubbed MASA (MDH-ATP synthase adapter). It's a beautiful example of lineage-specific innovation being incorporated directly into a conserved molecular machine.

1/ 🧵 Two classic mitochondrial pathways the TCA cycle and OXPHOS are taught as linked but distinct pathways. I’m happy to share our new work out in @cp-cell.bsky.social showing that in Acanthamoeba they're physically linked—with a TCA enzyme incorporated in ATP synthase. www.cell.com/cell/fulltex...

Excited to share our collaborative work characterizing a pathogenic mutation in Opa1 found in ADOA patients that began when Tom Schwarz @BostonChildrens presented a seminar @MGHMolBio biorxiv.org/content/10.1... @lukechao.bsky.social

5/ Our findings bring us closer to understanding the molecular mechanisms behind ADOA and open new avenues for developing targeted therapies to prevent neurodegeneration.

Excited to share our collaborative work characterizing a pathogenic mutation in Opa1 found in ADOA patients that began when Tom Schwarz @BostonChildrens presented a seminar @MGHMolBio biorxiv.org/content/10.1... @lukechao.bsky.social

3/ Using cryo-ET, we quantified architectural changes in mitochondrial ultrastructure, giving us detailed insights into how this pathogenic OPA1 mutation affect mitochondrial integrity at the nanoscale level.

Excited to share our collaborative work characterizing a pathogenic mutation in Opa1 found in ADOA patients that began when Tom Schwarz @BostonChildrens presented a seminar @MGHMolBio biorxiv.org/content/10.1... @lukechao.bsky.social

1/ ADOA, a common inherited optic neuropathy, leads to RGC degeneration and vision loss. It's primarily caused by mutations in the OPA1 gene, a key player in mitochondrial inner membrane dynamics.