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Curr Biol. 2018 Apr 23;28(8):1265-1272.e4. doi: 10.1016/j.cub.2018.02.048. Epub 2018 Mar 29.

A cAMP/PKA/Kinesin-1 Axis Promotes the Axonal Transport of Mitochondria in Aging Drosophila Neurons.

Author information

1
Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London SE5 9RX, UK. Electronic address: alessio.vagnoni@kcl.ac.uk.
2
Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address: sbullock@mrc-lmb.cam.ac.uk.

Abstract

Mitochondria play fundamental roles within cells, including energy provision, calcium homeostasis, and the regulation of apoptosis. The transport of mitochondria by microtubule-based motors is critical for neuronal structure and function. This process allows local requirements for mitochondrial functions to be met and also facilitates recycling of these organelles [1, 2]. An age-related reduction in mitochondrial transport has been observed in neurons of mammalian and non-mammalian organisms [3-6], and has been proposed to contribute to the broader decline in neuronal function that occurs during aging [3, 5-7]. However, the factors that influence mitochondrial transport in aging neurons are poorly understood. Here we provide evidence using the tractable Drosophila wing nerve system that the cyclic AMP/protein kinase A (cAMP/PKA) pathway promotes the axonal transport of mitochondria in adult neurons. The level of the catalytic subunit of PKA decreases during aging, and acute activation of the cAMP/PKA pathway in aged flies strongly stimulates mitochondrial motility. Thus, the age-related impairment of transport is reversible. The expression of many genes is increased by PKA activation in aged flies. However, our results indicate that elevated mitochondrial transport is due in part to upregulation of the heavy chain of the kinesin-1 motor, the level of which declines during aging. Our study identifies evolutionarily conserved factors that can strongly influence mitochondrial motility in aging neurons.

KEYWORDS:

Drosophila; PKA; aging; axonal transport; cAMP; kinesin-1; mitochondria

PMID:
29606421
PMCID:
PMC5912900
DOI:
10.1016/j.cub.2018.02.048
[Indexed for MEDLINE]
Free PMC Article

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