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

• Published in: Current biology Vol. 28; no. 8; pp. 1265 - 1272.e4
• Main Authors: Vagnoni, Alessio, Bullock, Simon L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 23.04.2018; Cell Press
• Subjects: Age Factors; aging; Animals; axonal transport; Axonal Transport - physiology; Axons - metabolism; cAMP; Cyclic AMP - metabolism; Cyclic AMP - physiology; Cyclic AMP-Dependent Protein Kinases - metabolism; Cyclic AMP-Dependent Protein Kinases - physiology; Drosophila; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; kinesin-1; Kinesins - metabolism; Kinesins - physiology; mitochondria; Mitochondria - metabolism; Mitochondria - physiology; Neurons - metabolism; Organelles - metabolism; PKA; kinesin-1; mitochondria; Drosophila; PKA; axonal transport; aging; cAMP
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2018.02.048

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. [Display omitted] •cAMP/PKA pathway promotes mitochondrial transport in adult Drosophila wing neurons•Pathway activation in aged flies suppresses age-related reduction in transport•Levels of PKAc and kinesin-1 motor decline during aging•Kinesin-1 upregulation is an important output of PKA activation in aged flies Vagnoni and Bullock use the Drosophila wing to investigate the regulation of mitochondrial transport in aging neurons. They discover that acute activation of the cAMP/PKA pathway can suppress an age-related decline in mitochondrial motility. This effect is due in part to upregulation of the kinesin-1 motor, levels of which decline during aging.