Symmetric arrangement of mitochondria:plasma membrane contacts between adjacent photoreceptor cells regulated by Opa1

Abstract

Mitochondria are known to play an essential role in photoreceptor function and wellbeing that enables normal healthy vision. Within photoreceptors they are elongated and extend most of the length inner segment, where they supply energy for protein synthesis and the phototransduction machinery in the outer segment as well as acting as a calcium store. Here we examined the arrangement of the mitochondria within the inner segment in detail using 3D electron microscopy techniques and show they are tethered to the plasma membrane in a highly specialised arrangement. This includes mitochondria running alongside each other in neighbouring inner segments, with evidence of alignment of the cristae openings. As the pathway by which photoreceptors meet their high energy demands is not fully understood, we propose this to be a mechanism to share metabolites and assist in maintaining homeostasis across the photoreceptor cell layer. In the extracellular space between photoreceptors, Muller glial processes were identified. Due to the often close proximity to the inner segment mitochondria, they may too play a role in the inner segment mitochondrial arrangement as well as metabolite shuttling. OPA1 is an important factor in mitochondrial homeostasis, including cristae remodelling; therefore, we examined the photoreceptors of a heterozygous Opa1 knock-out mouse model. The cristae structure in the Opa1+/- photoreceptors was not greatly affected, but there were morphological abnormalities and a reduction in mitochondria in contact with the inner segment plasma membrane. This indicates the importance of key regulators in maintaining this specialised photoreceptor mitochondrial arrangement.