title: Autophagy and mitophagy interplay in melanoma progression.
abstract: Autophagy, or self-eating, is the most extensively studied lysosomal degradation pathway for the recycling of obsolete or damaged cytoplasmic materials, including proteins and organelles. Although this pathway was initially thought to function as trafficking system for 'in bulk' degradation by the lysosomes of cytoplasmic material, it is now widely appreciated that cargo selection by the autophagic machinery is a major process underlying the cytoprotective or--possibly--pro-death functions ascribed to this catabolic process. Indeed increasing evidence suggests that in mammalian cells the removal of dysfunctional or aged mitochondria occurs through a selective degradation pathway known as 'mitophagy'. Due to the crucial role of mitochondria in energy metabolism, redox control and cell survival/death decision, deregulated mitophagy can potentially impact a variety of crucial cell autonomous and non-autonomous processes. Accumulating evidence indicates that during malignant transformation aggressive cancers hijack autophagy to preserve energy fitness and to acquire the plasticity required to adapt to the hostile microenvironment. However, whether and how mitophagy contributes to carcinogenesis, which pathways regulate this process in the cancer cells and how cancer cell-mitophagy impacts and modifies the tumor microenvironment and therapeutic responses, remain largely unanswered issues. In this review, we discuss novel paradigms and pathways regulating mitophagy in mammalian cells and the impact this process might have on one of the most dreadful human malignancies, melanoma.
authors.affiliation: Laboratory of Cell Death and Therapy, Department Cellular and Molecular Medicine, KU Leuven, Leuven B-3000, Belgium.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Maes
authors.affiliation: Laboratory of Cell Death and Therapy, Department Cellular and Molecular Medicine, KU Leuven, Leuven B-3000, Belgium. Electronic address: patrizia.agostinis@med.kuleuven.be.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agostinis
mesh_terms: D001343:Autophagy / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism*; D063306:Mitophagy / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
keywords: Anticancer therapy; Autophagy; Cancer; Melanoma; Mitophagy; Signaling