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biorxiv2026-09-02mitochondrial dynamicscomputationalstructural biology

PRISM stably paints mitochondria with four other organelles and returns 500-plus contact metrics per cell

A single PiggyBac-integrable cassette (PRISM: Plasmid-based Reporter for Intracellular Spectral Microscopy) stably labels mitochondria, Golgi, peroxisomes, endoplasmic reticulum, and lysosomes for spectral microscopy, then a modular pipeline extracts more than 500 morphology, distribution, pairwise, and higher-order contact metrics per cell. The authors use it to score cytoskeletal perturbation, phosphatidylinositol 4-phosphate redistribution after lysosomal damage, and organelle-network remodeling during Zika virus infection.

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Signal profile (abstract-level)

mitochondrial dynamics · computational · structural biology

Score 74/100BIORXIVhigh confidencemitochondrial dynamics
74
Importance
50
Mito signal
81
Dysfunction
83
Evidence
15
Translational

Editorial signal profile from the abstract (importance score, mito keywords, dysfunction tags, evidence density, translational cues). Not a figure reproduced from the preprint PDF.

Finding. PRISM (Plasmid-based Reporter for Intracellular Spectral Microscopy) is a PiggyBac cassette that stably paints mitochondria together with Golgi, peroxisomes, endoplasmic reticulum, and lysosomes, then returns more than 500 morphology, position, and contact metrics per cell.

Why this paper matters

Most mitochondrial imaging still treats the organelle as a soloist: area, aspect ratio, branch count. The biology that actually breaks in infection, lipid stress, and membrane-contact disease is a duet or a quintet. Mitochondria kiss ER, park next to lysosomes, and share fission labor with peroxisomes. Those events are hard to count reproducibly across cell types because the reporters do not travel together.

Love, Baskir, Nixon-Abell and colleagues ship a single integrable construct and a pipeline. The mitochondrial reason to care is not a new cristae gene. It is a coordinate system: the same cell yields mitochondrial shape and the contact graph that explains why that shape changed.

What they actually measured

Five unique fluorescent reporters, chosen for spectral microscopy, label Golgi, peroxisomes, ER, mitochondria, and lysosomes. PiggyBac integration is meant to make that set stable across passages and cell types, and the cassette is described as compatible with extra molecular or functional probes (so you can still add a calcium sensor or a cargo marker).

The analysis layer is the other half of the product. It extracts more than 500 metrics per cell: organelle morphology and distribution, plus pairwise and higher-order contacts. That last phrase matters. Pairwise mito-ER contacts are table stakes. Higher-order contacts are how you notice a three-way ER-mito-lysosome cluster after lysosomal damage.

They show the system three ways. Cytoskeletal perturbation asks whether the network geometry is actin- or microtubule-dependent. Lysosomal damage plus phosphatidylinositol 4-phosphate (PI(4)P) mapping asks whether lipid landmarks move when one organelle fails. Zika infection asks whether a virus that is famous for remodeling ER also moves mitochondria and the rest of the set. The abstract does not report which mitochondrial features dominate those screens. The claim is that the landscape is now countable.

How to read the score

This sits in the mid-70s: high confidence that a usable five-organelle reporter plus a fat feature table exists, moderate mitochondrial specificity because mitochondria are one channel of five. Methods papers that let other groups measure mito-ER-lysosome geometry are still more useful to this corpus than another unvalidated fission blot.

It is not a Zika mechanism paper and not a disease brief. Score it as infrastructure.

What to do with it

If you run mitochondrial morphology screens, ask whether your hit also moved ER or lysosome contacts. PRISM is built for that question. Wait for the pipeline and the reporter map before cloning it into a primary cell you cannot afford to perturb. Do not treat the Zika demo as evidence that mitochondria are the viral target. Treat it as proof the network can be scored during infection.

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Source preprint

PRISM: A Plasmid-based Reporter for Intracellular Spectral Microscopy

10.64898/2026.09.01.746207

Love FM, Baskir Z, Allen T, Thomas S, Coyle H, Al-Dam N, Williams S, Maib H, Irigoyen N, Nixon-Abell J.

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