Bringing It All Together: The Vital Role Of Motor Proteins In Autophagy

Introduction

Autophagy is a vital catabolic process in which damaged organelles and other cellular structures are targeted for degradation and recycling of their constituent components. It is important for quality control and cellular homeostasis but also has other recognized roles, such as in differentiation and development.^1,2 Broadly known as a “self-eating” phenomenon, autophagy is not a single pathway but actually encompasses three related mechanisms³ under complex regulatory control: macroautophagy (the subject of this newsletter), chaperone-mediated autophagy (where specific proteins are directed to lysosomes for degradation), and microautophagy, in which cellular material is directly sequestered by membrane invaginations in late endosomes or lysosomes.¹

Macroautophagy, hereafter referred to as autophagy and summarized in Figure 1, may operate as either a nonselective bulk process or by recognizing particular cargos through specific autophagy receptors (SARs);⁴ for example, as seen in the elimination of damaged mitochondria by mitophagy.⁵ Either way, the selected cargo is surrounded by a double-membrane vesicle known as an autophagosome that must then fuse with a lysosome to initiate enzymatic degradation and complete the autophagic process. As explained below, the fusion step requires coordinated vesicle trafficking that is mediated by the cytoskeleton and associated motor proteins through mechanisms that continue to be unraveled.⁶

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