A Protein-Centric Perspective of Autophagy and Apoptosis Signaling and Crosstalk in Health and Disease

Abstract

Autophagy and apoptosis are pivotal pro-survival mechanisms of multicellular organisms activated in response to a variety of external and internal cues. Specifically, autophagy entails the degradation of excessive or aberrant cellular components to restore cellular homeostasis and ensure cell survival, whereas apoptosis initiates programmed cell death that sacrifices a subgroup of cells to preserve the viability of the whole organism. While seemingly opposing forces, these two distinct yet interconnected mechanisms serve to constrain stress-induced damage, eliminate potential triggers of pathogenesis, and recycle biological building blocks to support new biosynthesis in a living cell or organism. Accordingly, autophagy and apoptosis are tuned by delicate and complex signaling cascades, and inappropriate activation or disruption of these pathways have been associated with disease phenotypes. This book chapter focuses on delineating critical promoters of these two distinct biological processes as well as their interdependent molecular crosstalk from a protein-centric perspective. To better appreciate their clinical relevance, we also highlight the role of autophagy, apoptosis, and their crosstalk in diseases spanning four distinct organ types: heart, liver, central nervous system, and skeletal muscle. While the biological impact and signaling pathways of autophagy and apoptosis have been well-established, present studies have only touched the tip of the iceberg regarding the complex interplay between these two processes. Therefore, further exploration of the autophagy-apoptosis crosstalk opens the door to fully understanding the precise molecular mechanisms in many diseases and developing more effective therapeutic approaches.