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bioRxiv · 10.1101/2025.01.21.634043

Protein Kinase C positively regulates peroxisome biogenesis by promoting peroxisome-endoplasmic reticulum interaction

Borisyuk, A.·Howman, C. M.·Pattabiraman, S.·Kaganovich, D.·Amen, T.
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Abstract

Peroxisomes carry out a diverse set of metabolic functions, including oxidation of very long-chained fatty acids, degradation of D-amino acids and hydrogen peroxide, and bile acid production. Many of these functions are upregulated on demand, therefore cells control peroxisome abundance, and by extension peroxisome function, in response to environmental and developmental cues. The mechanisms upregulating peroxisomes in mammalian cells have remained unclear. Here we identify a signaling regulatory network and a mechanism that coordinate cellular demand for peroxisomes and peroxisome abundance by regulating peroxisome proliferation. We show that protein kinase C (PKC) promotes peroxisome PEX11b-dependent formation. PKC activation leads to an increase in peroxisome formation, promoting peroxisome-ER contact site formation through inactivation of GSK3{beta}. We show that removal of VAPA and VAPB impairs peroxisome biogenesis and PKC regulation. Inhibition of PKC reduces peroxisome-ER interactions, leading to a decrease in peroxisome abundance. During neuronal differentiation, active PKC leads to a significant increase in peroxisome formation. We propose that peroxisomal regulation by transient active PKC signaling enables rapid and fine-tuned responses to the need for peroxisomal activity.

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Borisyuk, A., Howman, C. M., Pattabiraman, S., Kaganovich, D., Amen, T.. 2025-01-25. Protein Kinase C positively regulates peroxisome biogenesis by promoting peroxisome-endoplasmic reticulum interaction. https://doi.org/10.1101/2025.01.21.634043

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