Submitted by Penny Peck on Tue, 15/09/2026 - 13:34
Scientists from the MRC Mitochondrial Biology Unit have identified a previously unknown enzymatic reaction that cells use to produce a lipid needed to break down and recycle unwanted material.
The collaborative study, published in Nature Cell Biology, was led by Dr Kasparas Petkevicius. Key experimental contributions and technical expertise came jointly from Pradeep Sheokand, Denis Lacabanne in Edmund Kunji’s group and Andrew James in Mike Murphy’s group.
The lipid, bis(monoacylglycero)phosphate (BMP), is enriched in the internal membranes of lysosomes, the compartments where cells digest unwanted or damaged material. Although BMP is essential for lysosomal function, key steps in its production have remained unresolved.
The team identified the enzyme responsible for one of these steps as CLN8. Mutations in CLN8 gene cause a form of Batten disease, a group of childhood inherited lysosomal storage disorders that progressively damage the nervous system. Using biochemical and structural approaches, the researchers established how CLN8 produces a building block for BMP synthesis. This discovery explains why loss of CLN8 severely reduces BMP levels and connects its enzymatic function to lysosomal dysfunction in disease.
Importantly, supplying the missing building block restored BMP levels in CLN8-deficient cells and mice. In a zebrafish model of the disease, it also improved movement and reduced seizure-like brain activity. These findings demonstrate that the biochemical defect can be bypassed, providing an early basis for exploring approaches to treatment.
The work developed alongside an independent study led by Professor Robert Zimmermann at the University of Graz, Austria, which identified the same function of CLN8 using different approaches. An EMBO Scientific Exchange Grant enabled Johannes Breithofer, a PhD student in Zimmermann’s group and first author of the companion paper, to visit Kasparas’s laboratory and perform key experiments. This exchange helped bring the teams’ complementary expertise together and established an ongoing collaboration. The two studies are published back-to-back in Nature Cell Biology (links below).
The team gratefully acknowledges funding awarded to Kasparas Petkevicius by the Batten Disease Global Research Initiative, NCL Stiftung and the Academy of Medical Sciences’ Springboard scheme, which helped make this work possible.
Publication references:
Sheokand et al. The Batten disease protein CLN8 is a stereospecific acyltransferase in bis(monoacylglycero)phosphate biosynthesis. Nature Cell Biology 2026.
https://www.nature.com/articles/s41556-026-02061-0
Back-to-back companion paper:
Breithofer et al. Batten disease protein CLN8 enables a non-canonical phospholipid synthesis pathway. Nature Cell Biology 2026.
https://www.nature.com/articles/s41556-026-02059-8