{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T09:52:18Z","timestamp":1782208338397,"version":"3.54.5"},"reference-count":77,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autophagy-associated readouts in localized prostate cancer cannot be interpreted based on LC3, p62\/SQSTM1, or LC3 puncta alone. In line with the concept of autophagy as a stress-response system, this review proposes a flux-aware, organelle-centered framework for assigning biological meaning to autophagy-related changes under disease-relevant stress. The framework integrates oxidative burden, lysosomal competence, selective autophagy, mitophagy, ferritinophagy, p62\/SQSTM1-NRF2 signaling, ferroptosis-aware controls, and disease-stage context to distinguish four interpretive states: homeostatic quality control, adaptive tumor survival, blocked clearance, and stress-overload vulnerability. Flavonoid-associated responses are used as stress-test examples because they expose recurrent limitations in the field, including supraphysiologic exposures, limited metabolite realism, static-marker inflation, and insufficient assessment of lysosomal function. However, the framework is not restricted to dietary compounds; it applies to metabolic, pharmacological, inflammatory, androgen-related, radiation-associated, or therapy-induced perturbations in which autophagy-associated markers are altered without resolution of flux or organelle function. By linking autophagosome formation, cargo turnover, lysosomal acidification, redox buffering, and phenotype-level endpoints, this review defines a practical evidence hierarchy for interpreting autophagy in localized prostate cancer and for prioritizing translational vulnerabilities arising from organelle crosstalk. This contribution is primarily conceptual and is operationalized methodologically through flux-based evaluation criteria and translationally through disease-window-specific study-design recommendations.<\/jats:p>","DOI":"10.3390\/cells15131134","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T08:19:52Z","timestamp":1782202792000},"page":"1134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autophagy Stress Responses in Localized Prostate Cancer: A Flux-Aware Framework for Disease-Relevant Interpretation"],"prefix":"10.3390","volume":"15","author":[{"given":"Zaira Edith","family":"Hern\u00e1ndez-Ram\u00edrez","sequence":"first","affiliation":[{"name":"Research Division, Hospital Ju\u00e1rez de M\u00e9xico, Mexico City 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6240-3468","authenticated-orcid":false,"given":"Enoc Mariano Cort\u00e9s","family":"Malag\u00f3n","sequence":"additional","affiliation":[{"name":"Research Division, Hospital Ju\u00e1rez de M\u00e9xico, Mexico City 07760, Mexico"},{"name":"Genetic Laboratory, Hospital Nacional Homeop\u00e1tico, Mexico City 06800, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-6248","authenticated-orcid":false,"given":"Jonathan","family":"Puente-Rivera","sequence":"additional","affiliation":[{"name":"Research Division, Hospital Ju\u00e1rez de M\u00e9xico, Mexico City 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Flores-Estrada","sequence":"additional","affiliation":[{"name":"Research Division, Hospital Ju\u00e1rez de M\u00e9xico, Mexico City 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lo Greco, M.C., Marletta, G., Marano, G., Fazio, A., Buffettino, E., Iudica, A., Liardo, R.L.E., Milazzotto, R., Foti, P.V., and Palmucci, S. 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