Proceedings of The Physiological Society

Mitochondria: Form and function (London, UK) (2017) Proc Physiol Soc 38, PC06

Poster Communications

Regulation of mitochondria by ARMCX proteins in retinal pigment epithelial cells

A. Kirby1, M. Yang1, M. Radeke2, P. Turowski1

1. Institute of Ophthalmology, University College London, London, United Kingdom. 2. Neuroscience Research Institute, UCSB, Santa Barbara, California, United States.

Situated at the back of the retina, the retinal pigment epithelium (RPE) is a dynamic tissue, which is essential for visual function. It is arguably the most metabolically active tissue in the human body and co-ordinates numerous processes to aid photoreceptor function, including phagocytosis of outer segments, ion transport, light absorption and photo pigment recycling. It also protects the neuroretina by acting as physical barrier and regulating oxidative stress. RPE mitochondria are situated in highly organised basolateral membrane infolds in close apposition to the choroidal blood supply. Their number and organisation decreases with age, and this is significantly worsened in age-related macular degeneration (AMD)1. Indeed, mitochondrial dysfunction has been implicated in the pathogenesis of AMD, where gene expression analysis indicates that expression of ARMCX3, a regulator of mitochondrial trafficking in neurons2, is down-regulated in the early stages of the disease3. All six gene products of the ARMCX family are specific to Eutherian mammals and, based on finding from ARMCX3, are thought to be involved in mitochondrial trafficking and dynamics2. Differentiation of the RPE causes an up-regulation of ARMCX expression4, indicative of an important role in the mature tissue. We hypothesised that ARMCX proteins are key to RPE function by regulating mitochondrial function, in particular their dynamics. To this end, we have overexpressed GFP-tagged ARMCX1-3 and ARMCX5-6 in cultured RPE cells and found that all ARMCXs except ARMCX5 co-localised with mitochondria. Co-localisation was also confirmed for endogenous ARMCX by indirect immunostaining. Time-lapse fluorescence microscopy revealed that overexpression of ARMCX1-3 or ARMCX6 led to collapse of mitochondrial networks and induced reduced trafficking. These results provide evidence of ARMCX proteins as regulators of mitochondrial dynamics in the RPE, and suggest that down-regulation of ARMCX may contribute to the pathogenesis of AMD, through dysregulation of the mitochondrial network.

Where applicable, experiments conform with Society ethical requirements