Journal
BIOLOGY OPEN
Volume 9, Issue 1, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.047530
Keywords
Drosophila; Organelle contacts; Mitochondria; Endoplasmic reticulum; Alzheimer's disease
Categories
Funding
- UK Medical Research Council [MC_UU_00025/3 [RG94521]]
- MRC [MC_U132674518, MC_UU_00025/3] Funding Source: UKRI
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Eukaryotic cells are complex systems containing internal compartments with specialised functions. Among these compartments, the endoplasmic reticulum (ER) plays a major role in processing proteins for modification and delivery to other organelles, whereas mitochondria generate energy in the form of ATP. Mitochondria and the ER form physical interactions, defined as mitochondria-ER contact sites (MERCs) to exchange metabolites such as calcium ions (Ca2+) and lipids. Sites of contact between mitochondria and the ER can regulate biological processes such as ATP generation and mitochondrial division. The interactions between mitochondria and the ER are dynamic and respond to the metabolic state of cells. Changes in MERCs have been linked to metabolic pathologies such as diabetes, neurodegenerative diseases and sleep disruption. Here we explored the consequences of increasing contacts between mitochondria and the ER in flies using a synthetic linker. We showed that enhancing MERCs increases locomotion and extends lifespan. We also showed that, in a Drosophila model of Alzheimer's disease linked to toxic amyloid beta (A beta), linker expression can suppress motor impairment and extend lifespan. We condude that strategies for increasing contacts between mitochondria and the ER may improve symptoms of diseases associated with mitochondria dysfunction. A video abstract for this article is available at https://youtu.be/_YWA4oKZkes. This article has an associated First Person interview with the first author of the paper.
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