Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy

Abstract

Research in biomedical sciences has changed dramatically over the past fifty years. There is no doubt that the discovery of apoptosis and autophagy as two highly synchronized and regulated mechanisms in cellular homeostasis are among the most important discoveries in these decades. Along with the advancement in molecular biology, identifying the genetic players in apoptosis and autophagy has shed light on our understanding of their function in physiological and pathological conditions. In this review, we first describe the history of key discoveries in apoptosis with a molecular insight and continue with apoptosis pathways and their regulation. We touch upon the role of apoptosis in human health and its malfunction in several diseases. We discuss the path to the morphological and molecular discovery of autophagy. Moreover, we dive deep into the precise regulation of autophagy and recent findings from basic research to clinical applications of autophagy modulation in human health and illnesses and the available therapies for many diseases caused by impaired autophagy. We conclude with the exciting crosstalk between apoptosis and autophagy, from the early discoveries to recent findings.

Programmed cell death and lipid metabolism of macrophages in NAFLD

“…Apoptosis is a Caspase-dependent cell death that includes intrinsic pathways induced by DNA damage, ROS accumulation, and endoplasmic reticulum stress (also known as the mitochondrial pathway) as well as exogenous apoptotic pathways initiated by the binding of other cellular soluble or cell surface ligands including TNF, FasL, or TRAIL to death receptors ( 95 ). The Caspase family is a family of evolutionarily conserved cysteine-dependent endonucleases that are primarily involved in cell death and inflammatory responses.…”

Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease

“…Apoptosis, a programme of controlled cell death [ 434 ], may have a role in the neuronal cell death associated with AD, based on evidence of increased apoptosis in the AD brain compared with the normal brain [ 435 , 436 ]. 25 plant species in this study had reports of anti-apoptotic bioactivity (Additional file 4 : Table S4).…”

Protective effect of sialyllactose on the intestinal epithelium in weaned pigs upon enterotoxigenic Escherichia coli challenge

“…44 Proteolytic activation of Caspase 3 triggers cascade activation of caspases, predominantly Caspase 9 , thereby initiating apoptosis. 45 Moreover, Bcl-2 and its relatives can also regulate apoptosis in response to Caspase 3 activation. 46,47 Previous studies have shown that ETEC infection leads to increased apoptosis of the intestinal epithelial cells, which will contribute to the disruption of the intestinal epithelium.…”

“…44 Proteolytic activation of Caspase 3 triggers cascade activation of caspases, predominantly Caspase 9, thereby initiating apoptosis. 45 Moreover, Bcl-2 and its relatives can also regulate apoptosis in response to Caspase 3 activation. 46,47 Previous studies have shown that ETEC infec-…”