Hartwig C, Méndez GM, Bhattacharjee S, Vrailas-Mortimer AD, Zlatic SA, Freeman AAH, Gokhale A, Concilli M, Werner E, Sapp Savas C, Rudin-Rush S, Palmer L, Shearing N, Margewich L, McArthy J, Taylor S, Roberts B, Lupashin V, Polishchuk RS, Cox DN, Jorquera RA, Faundez V. Golgi-Dependent Copper Homeostasis Sustains Synaptic Development and Mitochondrial Content. J Neurosci. 2020 Nov 17:JN-RM-1284-20. doi: 10.1523/JNEUROSCI.1284-20.2020. PMID: 33208468.
From the abstract:
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 complex, or 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. ... 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. ... These findings suggest communication between the Golgi apparatus and mitochondria through homeostatically controlled cellular copper levels and copper-dependent enzymatic activities in both organelles.
