Autophagy and mitophagy in dermatological disease - a comprehensive review from molecular pathways to therapeutic frontiers

Sep 30, 2026

Autophagy, the cell’s recycling and quality-control program, shapes multiple layers of skin biology, from keratinocyte envelope formation and melanocyte control of pigment synthesis and oxidative stress to coordinated immune, appendageal, defence, repair, and hair-follicle cycling. This review links core molecular mechanisms, including ULK1 signalling, Beclin-1/VPS34 nucleation, LC3B lipidation and selective mitophagy, to dysregulation in psoriasis, atopic dermatitis, vitiligo, melanoma, non-melanoma cancers, infections, wound repair and ageing. It also surveys therapeutic strategies and biomarker prospects for precision intervention.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Introduction

Skin barrier function and cellular quality-control

Autophagy as a homeostasis and adaptation pathway

Forms of autophagy: macro-, micro-, and CMA

Molecular mechanisms and selective mitophagy (overview)

D’Ambrosio et al. Biology Direct (2026) 21:4 [https://doi.org/10.1186/s13062-025-00703-1](https://doi.org/10.1186/s13062-025-00703-1) Biology Direct REVIEW Open Access Autophagy and mitophagy in dermatological disease: a comprehensive review from molecular pathways to therapeutic frontiers Luca D’Ambrosio 1†, Maria Elisabetta Greco2†, Maurizio Forte 1, Daniele Vecchio6, Sonia Schiavon 1,6, Flavio Di Nonno 1, Shazia Tahir8, Vittorio Picchio6, Claudia Cozzolino6, Gianmarco Sarto5, Marco Bernardi6,9, Luigi Spadafora6,9, Beatrice Simeone5, Mattia Vinciguerra3,4, Sebastiano Sciarretta 1,5,6, Giacomo Frati 1,6, Ernesto Greco4, Concetta Potenza6,7, Ilaria Proietti6,7, Jacopo Morroni 10, Elisa Dietrich6† and Leonardo Schirone 1,4*† Abstract Autophagy – the cell’s built-in recycling and quality-control programme – touches every layer of cutaneous biology. In keratinocytes it sculpts the cornified envelope; in melanocytes it balances pigment synthesis and oxidative stress; in immune and appendageal cells it fine-tunes defence, repair and hair-follicle cycling. When this choreography falters, skin disorders emerge. This review journeys from basic mechanisms (ULK1 signalling, Beclin-1/VPS34 nucleation, LC3B lipidation, selective mitophagy) to their fingerprints in health and disease. We dissect how autophagy malfunctions drive psoriasis hyper-proliferation, atopic-dermatitis barrier leakiness, vitiligo depigmentation and the metabolic rewiring of melanoma. Non-melanoma cancers, infectious dermatoses, wound repair, ageing and photo-damage are mapped onto the same autophagic atlas. Therapeutically, the pathway is a double-edged sword. mTOR or caloric-restriction mimetics jump-start a protective flux; chloroquine derivativesand ULK1 blockers clip tumour survival circuits; cannabinoids, photodynamic therapy and immune-checkpoint combinations exploit context-specific toggling between induction and brake. Emerging biomarkers (LC3B-II, p62, AMBRA1) promise patient-stratified interventions. By weaving together molecular detail, pre-clinical insight and clinical translation, we show why autophagy is no longer a backstage process but a star player in dermatology – and how targeting its switches could reshape future treatment algorithms. Keywords Autophagy, Mitophagy, Skin disorders, Dermatological disease, Skin homeostasis, Immunodermatology †Luca D’Ambrosio, Maria Elisabetta Greco, Elisa Dietrich, and Leonardo Schirone equal contribution. *Correspondence: Leonardo Schirone [leonardo.schirone@unier.it](leonardo.schirone@unier.it) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. D’Ambrosio et al. Biology Direct (2026) 21:4 Introduction The skin is the largest organ of the human body and serves as the primary barrier between the internal milieu and the external environment. Beyond its role in physical protection, the skin regulates ther

FAQs

What role does autophagy play in skin biology?

Autophagy contributes to cutaneous homeostasis by regulating processes such as keratinocyte cornified envelope formation, melanocyte pigment synthesis and oxidative-stress balance, and tuning defence, repair, and hair-follicle cycling.

Which molecular components are highlighted as key drivers of autophagy?

The review focuses on core mechanisms including ULK1 signalling, Beclin-1/VPS34 nucleation, and LC3B lipidation, alongside selective mitophagy pathways.

How can autophagy dysregulation relate to dermatological diseases?

When the autophagic programme falters, skin disorders can emerge; the review connects dysfunction to conditions such as psoriasis, atopic dermatitis, vitiligo and metabolic rewiring in melanoma, and extends mapping to other dermatologic contexts.

Sep 30, 2026

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