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← All articlesEditorial brief · abstract-levelScore 86/100Confidence high
biorxiv2026-10-02calciumfertilitymetabolismion channels

Human sperm feed CatSper calcium into the mitochondrial uniporter to turn on respiration and hyperactivated motility

In paired non-capacitated and capacitated sperm from normozoospermic donors, capacitation raises respiratory control ratio, coupling efficiency, mitochondrial membrane potential, and mitochondrial calcium. The calcium rise needs extracellular calcium, CatSper, and the mitochondrial calcium uniporter (MCU). Block CatSper or MCU and hyperactivated motility falls; progressive and total motility, and the acrosome reaction, do not.

Mito.news · at a glance

Signal profile (abstract-level)

calcium · fertility · metabolism · ion channels

Score 86/100BIORXIVhigh confidencecalcium
86
Importance
50
Mito signal
39
Dysfunction
75
Evidence
30
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. Human sperm load mitochondria with CatSper calcium when they capacitate, and that load is how they start to swim in the hyperactivated style. Irigoyen, Santi and colleagues take paired samples from normozoospermic donors, before and after capacitation. Respiratory control ratio, coupling efficiency, membrane potential, and mitochondrial calcium all rise. The calcium rise dies if you remove extracellular calcium, block CatSper, or block the mitochondrial calcium uniporter. The same two blocks blunt the membrane-potential rise and cut hyperactivated motility. Progressive motility and total motility stay up. Poison the mitochondrion and hyperactivation falls; the acrosome reaction does not. The mouse path is conserved.

Why this paper matters

Capacitation has been two posters on one wall: CatSper and mitochondria. This preprint draws the arrow. For clinics it says hyperactivation, not the acrosome, is the mitochondrial readout. For contraception or fertility rescue it names MCU as a second handle next to CatSper.

What they actually measured

Paired human donors, four mitochondrial assays, two channel inhibitors, motility classes, acrosome. No IVF dish.

How to read the score

Mid 80s. Human, paired, conserved mechanism, clean motility split. Confidence is high for the pharmacology.

Caveats

Drugs, not mutants. Fertile donors. No oocyte.

What to do with it

If you score human capacitation, add mitochondrial calcium and RCR next to hyperactivation. If you drug CatSper, expect MCU and membrane potential to follow. Do not treat MCU inhibitors as a proven contraceptive from this brief.

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Source preprint

Mitochondrial Calcium Uptake Promotes Mitochondrial Activation and Hyperactivated Motility During Human Sperm Capacitation

10.64898/2026.09.28.755036

Irigoyen P, Ferreira JJ, Cassina A, Bhagwat S, Peramsetty N, Sapiro R, Santi CM.

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