Evidence map›Paper›PMID 40100494›Full record

ArticleMolecular neurobiology2025

Retinal Pigment Epithelium and Monocytes' Mitochondrial Control of Ferroptosis and its Relevance to Age-Related Macular Degeneration.

Mithalesh Kumar Singh, Lata Singh, Shari Atilano, Marilyn Chwa, Nasim Salimiaghdam, M Cristina Kenney

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Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Mithalesh Kumar SinghDirector of Mitochondria Research Laboratory, Gavin Herbert Eye Institute, University of California Irvine, 843 Health Science Rd, Hewitt Hall, Room 2028 , Irvine, CA, 92697, USA. mithalesh.singh@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-1812-9860
Lata SinghDepartment of Pediatrics, All India Institute of Medical Institute, New Delhi, 110029, India.
Shari AtilanoDirector of Mitochondria Research Laboratory, Gavin Herbert Eye Institute, University of California Irvine, 843 Health Science Rd, Hewitt Hall, Room 2028 , Irvine, CA, 92697, USA.
Marilyn ChwaDirector of Mitochondria Research Laboratory, Gavin Herbert Eye Institute, University of California Irvine, 843 Health Science Rd, Hewitt Hall, Room 2028 , Irvine, CA, 92697, USA.
Nasim SalimiaghdamDirector of Mitochondria Research Laboratory, Gavin Herbert Eye Institute, University of California Irvine, 843 Health Science Rd, Hewitt Hall, Room 2028 , Irvine, CA, 92697, USA.
M Cristina KenneyDirector of Mitochondria Research Laboratory, Gavin Herbert Eye Institute, University of California Irvine, 843 Health Science Rd, Hewitt Hall, Room 2028 , Irvine, CA, 92697, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Age-related macular degeneration (AMD) is the leading cause of vision impairment among older aged people. Recent studies have indicated that focusing on the underlying mechanism of ferroptosis (a form of iron-dependent cell death) could be crucial in understanding the progression of AMD, as it is strongly linked with inflammation. However, the specific dependence of ferroptosis on the mitochondria in the retinal pigment epithelium (RPE) and its surrounding immune cells remains unclear. In this study, we showed that mitochondria were required for the proliferation and maintenance of the RPE by regulating the expression of genes implicated in both pro- and antiferroptosis activities. Under chemically induced hypoxic conditions, Wt-ARPE-19 cells (basal mitochondrial level) increased the expression of genes linked with antiferroptotic activity. In contrast, rho0-ARPE-19 cells (mitochondria depleted) did not stimulate either pro- or antiferroptosis gene expression. However, diff-ARPE-19 cells (abundant in mitochondria) presented an improved proferroptotic activity. Furthermore, we demonstrated that mitochondria regulated monocyte differentiation into macrophages, resulting in differential expression of pro- and antiferroptotic factors. Through a direct coculture approach, the absence of mitochondria in ARPE-19 cells was shown to influences monocyte differentiation toward an inflammatory phenotype. This differentiation might increase ferroptosis activity. Transmitochondrial cybrids derived from patients with dry AMD and age-matched controls without dry AMD presented elevated mtDNA copy numbers, leading to increased ferritinophagy and increased levels of polyunsaturated fatty acids. These data highlighted that ferroptosis was partly regulated by mitochondria and that understanding the mechanisms governing the relationship between mitochondria and ferroptosis may open new potential avenues for managing dry AMD.

Indexed as

FerroptosisMacular DegenerationMitochondriaMonocytesRetinal Pigment EpitheliumCell DifferentiationCell LineHumansCybridsDifferentiated ARPE-19Dry-age macular degenerationFerroptosisMitochondriaMonocytesrho0

Identifiers

PMID40100494

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.