Role of Mitochondrial Dysfunction in UV-Induced Photoaging and Skin Cancers

Abstract

Ultraviolet radiation (UVR) is the most detrimental external factor that induces acute photodamage, photoaging and skin cancers, with complex underlying molecular mechanisms initiated mainly by increased DNA damage and reactive oxygen species (ROS) generation. Mitochondria are the main organelles in skin cells that produce ROS and energy and regulate various physiological and pathological signalling pathways. Continuous UVR on human skin can induce mitochondrial DNA mutations and excessive ROS production, creating feedback between each other and subsequently causing a reduction in mitochondrial membrane potential (MMP) and respiratory capacity. Deficiencies in mitochondrial function can induce apoptosis, mitophagy and senescence, resulting in UVR-induced skin photodamage and photoaging. Mitochondrial biogenesis and metabolic pathways play critical roles in the progression of skin cancers, particularly melanoma, which is the most malignant and infrequent type of cancer. In this review, we describe the recent advances in determining the intimate relationship between mitochondrial function and UVR-induced skin damage, suggesting potential molecular candidates and novel chemical/natural components to protect the skin from photoaging and skin cancers via mitochondrial targeting mechanisms.