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J Cell Sci. 2016 Jan 1;129(1):178-90. doi: 10.1242/jcs.179184. Epub 2015 Nov 23.

Reducing Lissencephaly-1 levels augments mitochondrial transport and has a protective effect in adult Drosophila neurons.

Author information

1
Division of Cell Biology, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
2
Division of Cell Biology, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK sbullock@mrc-lmb.cam.ac.uk.

Abstract

Defective transport of mitochondria in axons is implicated in the pathogenesis of several age-associated neurodegenerative diseases. However, the regulation and function of axonal mitochondrial motility during normal ageing is poorly understood. Here, we use novel imaging procedures to characterise axonal transport of these organelles in the adult Drosophila wing nerve. During early adult life there is a boost and progressive decline in the proportion of mitochondria that are motile, which is not due to general changes in cargo transport. Experimental inhibition of the mitochondrial transport machinery specifically in adulthood accelerates the appearance of focal protein accumulations in ageing axons, which is suggestive of defects in protein homeostasis. Unexpectedly, lowering levels of Lissencephaly-1 (Lis1), a dynein motor co-factor, augments axonal mitochondrial transport in ageing wing neurons. Lis1 mutations suppress focal protein accumulations in ageing neurons, including those caused by interfering with the mitochondrial transport machinery. Our data provide new insights into the dynamics of mitochondrial motility in adult neurons in vivo, identify Lis1 as a negative regulator of transport of these organelles, and provide evidence of a link between mitochondrial movement and neuronal protein homeostasis.

KEYWORDS:

Axonal transport; Drosophila; Lissencephaly-1; Mitochondria

PMID:
26598558
PMCID:
PMC4732301
DOI:
10.1242/jcs.179184
[Indexed for MEDLINE]
Free PMC Article

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