How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration

Aparna Lakkaraju; Patricia Boya; Marie Csete; Deborah A Ferrington; James B Hurley; Alfredo A Sadun; Peng Shang; Ruchi Sharma; Debasish Sinha; Marius Ueffing; Susan E Brockerhoff

doi:10.1016/j.exer.2024.110219

How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration

Exp Eye Res. 2024 Dec 22:251:110219. doi: 10.1016/j.exer.2024.110219. Online ahead of print.

Authors

Affiliations

¹ Departments of Ophthalmology and Anatomy, School of Medicine, University of California, San Francisco, San Francisco, CA, 94143, USA; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, San Francisco, CA, 94143, USA. Electronic address: [email protected].
² Department of Neuroscience and Movement Science, Faculty of Science and Medicine, University of Fribourg, Fribourg, 1700, Switzerland.
³ OkuloVision Inc., Pasadena, CA, USA.
⁴ Doheny Eye Institute, Los Angeles, CA, USA; Department of Ophthalmology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
⁵ Departments of Biochemistry and Ophthalmology, University of Washington, Seattle, WA, USA.
⁶ Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
⁷ Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department for Ophthalmology, Institute for Ophthalmic Research, University Eye Clinic, Eberhard Karls University of Tübingen, Tübingen, Germany.
⁹ Departments of Biochemistry and Ophthalmology, University of Washington, Seattle, WA, USA. Electronic address: [email protected].

PMID: 39716681
DOI: 10.1016/j.exer.2024.110219

Abstract

Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE). However, how these occur, and how they relate to organelle function both with the RPE and potentially the photoreceptors are fundamental, unresolved questions in AMD biology. Here, we report the discussions of the "Mitochondria, Lysosomes, and other Organelle Interactions" task group of the 2024 Ryan Initiative for Macular Research (RIMR). Our group focused on understanding the interplay between cellular organelles in maintaining homeostasis in the RPE and photoreceptors, how this could be derailed to promote AMD, and identifying where these pathways could potentially be targeted therapeutically.

Keywords: Bioenergetics; Oxidative stress; Photoreceptors; Retinal pigment epithelium; Therapeutics.

Publication types

Review