Golgi-dependent copper homeostasis sustains synaptic development and mitochondrial content

Cortnie Hartwig, Gretchen MacÍas Méndez, Shatabdi Bhattacharjee, Alysia D. Vrailas-Mortimer, Stephanie A. Zlatic, Amanda A.H. Freeman, Avanti Gokhale, Mafalda Concilli, Erica Werner, Christie Sapp Savas, Samantha Rudin-Rush, Laura Palmer, Nicole Shearing, Lindsey Margewich, Jacob McArthy, Savanah Taylor, Blaine Roberts, Vladimir Lupashin, Roman S. Polishchuk, Daniel N. CoxRamon A. Jorquera, Victor Faundez

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

16 Citas (Scopus)


Rare genetic diseases preponderantly affect the nervous system causing neurodegeneration to neurodevelopmental disorders. This is the case for both Menkes and Wilson disease, arising from mutations in ATP7A and ATP7B, respectively. The ATP7A and ATP7B proteins localize to the Golgi and regulate copper homeostasis. We demonstrate genetic and biochemical interactions between ATP7 paralogs with the conserved oligomeric Golgi (COG) complex, a Golgi apparatus vesicular tether. Disruption of Drosophila copper homeostasis by ATP7 tissue-specific transgenic expression caused alterations in epidermis, aminergic, sensory, and motor neurons. Prominent among neuronal phenotypes was a decreased mitochondrial content at synapses, a phenotype that paralleled with alterations of synaptic morphology, transmission, and plasticity. These neuronal and synaptic phenotypes caused by transgenic expression of ATP7 were rescued by downregulation of COG complex subunits. We conclude that the integrity of Golgi-dependent copper homeostasis mechanisms, requiring ATP7 and COG, are necessary to maintain mitochondria functional integrity and localization to synapses.

Idioma originalInglés
Páginas (desde-hasta)215-233
Número de páginas19
PublicaciónJournal of Neuroscience
EstadoPublicada - 13 ene. 2021

Áreas temáticas de ASJC Scopus

  • Neurociencias General


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