PE homeostasis rebalanced through mitochondria-ER lipid exchange prevents retinal degeneration in Drosophila

English version

Autoři: Haifang Zhao ^aff001; Tao Wang ^aff001
Působiště autorů: National Institute of Biological Sciences, Beijing, China ^aff001; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China ^aff002
Vyšlo v časopise: PE homeostasis rebalanced through mitochondria-ER lipid exchange prevents retinal degeneration in Drosophila. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009070
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009070

Souhrn

The major glycerophospholipid phosphatidylethanolamine (PE) in the nervous system is essential for neural development and function. There are two major PE synthesis pathways, the CDP-ethanolamine pathway in the endoplasmic reticulum (ER) and the phosphatidylserine decarboxylase (PSD) pathway in mitochondria. However, the role played by mitochondrial PE synthesis in maintaining cellular PE homeostasis is unknown. Here, we show that Drosophila pect (phosphoethanolamine cytidylyltransferase) mutants lacking the CDP-ethanolamine pathway, exhibited alterations in phospholipid composition, defective phototransduction, and retinal degeneration. Induction of the PSD pathway fully restored levels and composition of cellular PE, thus rescued the retinal degeneration and defective visual responses in pect mutants. Disrupting lipid exchange between mitochondria and ER blocked the ability of PSD to rescue pect mutant phenotypes. These findings provide direct evidence that the synthesis of PE in mitochondria contributes to cellular PE homeostasis, and suggest the induction of mitochondrial PE synthesis as a promising therapeutic approach for disorders associated with PE deficiency.

Klíčová slova:

Drosophila melanogaster – Eyes – Lipid analysis – Mitochondria – Phospholipids – Photoreceptors – Retina – Retinal degeneration

Zdroje

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