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← All articlesEditorial brief · abstract-levelScore 76/100Confidence high
biorxiv2026-09-03bioenergeticsinfectionfungitherapeutics

Cryptococcal Yck2 sits on mitochondria and the proton pump, and losing it raises mitochondrial ROS

The casein kinase Yck2 in Cryptococcus neoformans, already a druggable virulence node, proximity-labels mitochondrial proteins and the plasma-membrane H+ ATPase Pma1. Without Yck2, cells are sensitive to mitochondrial inhibitors, make more mitochondrial ROS, and run a higher intracellular pH. Cell wall, drugs, and temperature phenotypes now have an organelle-and-pH fuse.

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Signal profile (abstract-level)

bioenergetics · infection · fungi · therapeutics

Score 76/100BIORXIVhigh confidencebioenergetics
76
Importance
50
Mito signal
67
Dysfunction
75
Evidence
70
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. Delete the Cryptococcus casein kinase Yck2 and the fungus loses cell-wall disguise, heat tolerance, and drug composure. Bloom, Panepinto and colleagues ask why. Proximity labeling puts Yck2 next to mitochondrial proteins and the essential proton pump Pma1. The kinase is in mitochondrial fractions. Without it, mitochondrial inhibitors bite harder, mitochondrial ROS rises, and pHluorin says the cell is too alkaline.

Score 76. Druggable fungal kinase with a mitochondrial and pH mechanism. High confidence for the phenotypes as stated.

What to do with it If you optimize Yck2 inhibitors, add mtROS and pH, not only wall stains.

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Source preprint

Yck2 links mitochondrial function and pH homeostasis to cell wall remodeling and antifungal susceptibility in Cryptococcus neoformans

10.64898/2026.09.02.749035

Bloom AL, Goich D, Mendelson E, Chen S, Mazzaferro M, Qu J, Panepinto JC.

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