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

Significance Mitochondria play an essential role in the homeostasis of the highly energy-demanding photoreceptors and enable normal vision. We used 3D electron microscopy to show that the mitochondria in the photoreceptor inner segment are tethered to the plasma membrane in a highly specialized arrangement. This includes mitochondria running alongside each other in neighboring inner segments, with evidence of alignment of the cristae openings. The cristae structure was not greatly affected in photoreceptors of a heterozygous Opa1 knockout mouse model, but the mitochondria were enlarged and had reduced alignment to neighboring inner-segment mitochondria. This leads us to propose that mitochondria are arranged to share metabolites and assist in maintaining homeostasis across the photoreceptor cell layer.
Mitochondria are known to play an essential role in photoreceptor function and survival that enables normal vision. Within photoreceptors, mitochondria are elongated and extend most of the inner-segment length, 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 three-dimensional (3D) electron microscopy techniques and show they are tethered to the plasma membrane in a highly specialized arrangement. Remarkably, mitochondria and their cristae openings align with those of neighboring inner segments. 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, Müller 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 remodeling; therefore, we examined the photoreceptors of a heterozygous Opa1 knockout mouse model. The cristae structure in the Opa1+/− photoreceptors was not greatly affected, but the mitochondria were enlarged and had reduced alignment to neighboring inner-segment mitochondria. This indicates the importance of key regulators in maintaining this specialized photoreceptor mitochondrial arrangement.