CHIARA DE LEONIBUS*, CARMINE SETTEMBRE
*Corresponding author
Telethon Institute of Genetics and Medicine, Pozzuoli, Napoli, Italy

Abstract

Cellular clearance is emerging as a fundamental process required by all cells and in all species to regulate important physiological processes, including aging and organism development. In mammals, a main clearing process is “autophagy”, a finely regulated cellular process committed to the degradation of different substrates, including collagen. Collagen is the most abundant protein in our body, and it has a great medical relevance in treating bones and joints complications along with tissue regeneration and wound healing. Herein we describe the principal genetic disorders of collagen formation, or collagenopathies, including Osteogenesis Imperfecta (OI), Ehlers-Danlos syndrome (EDS) and Spondyloepiphyseal dysplasia congenita (SEDC). We further discuss on the most recent research findings made on autophagy and on the cellular clearing processes along with the idea to tackle this process to find novel pharmacological approaches to treat collagenopathies.

INTRODUCTION
Cellular clearance is increasingly emerging as a fundamental process required by all cells and in all species to regulate important physiological processes, including aging and organism development. In mammals, “autophagy” represents a main and finely regulated degradative process committed to the sequestration of cellular substrates in double-membrane vesicles (or autophagosomes) that eventually fuse with the lysosome, a specialized organelle with digestive capacity (Figure 1). Proteins and entire or portions of organelles can be targeted to autophagy via receptor-mediated processes. A remarkable example is represented by “ER-phagy”, a selective receptor-mediated form of autophagy in which fragments of the endoplasmic reticulum (ER) are delivered by autophagosomes to the lysosomes for degradation (1). Notably, the ER represents the largest cellular organelle with fundamental roles, secreting one third of the human proteins. However, this process can regularly lead to the accumulation of unfolded proteins within the ER lumen, consequent to an inefficient protein folding, which triggers cellular stress, namely ER stress, and contribute ...