The crosstalk between autophagy and apoptosis: where does this lead?

Abstract

Recent advances in the understanding of the molecular processes contributing to autophagy have provided insight into the relationship between autophagy and apoptosis. In contrast to the concept of "autophagic cell death," accumulating evidence suggests that autophagy serves a largely cytoprotective role in physiologically relevant conditions. The cytoprotective function of autophagy is mediated in many circumstances by negative modulation of apoptosis. Apoptotic signaling, in turn, serves to inhibit autophagy. While the mechanisms mediating the complex counter-regulation of apoptosis and autophagy are not yet fully understood, important points of crosstalk include the interactions between Beclin-1 and Bcl-2/Bcl-xL and between FADD and Atg5, caspase- and calpain-mediated cleavage of autophagy-related proteins, and autophagic degradation of caspases. Continued investigation of these and other means of crosstalk between apoptosis and autophagy is necessary to elucidate the mechanisms controlling the balance between survival and death both under normal conditions and in diseases including cancer.

Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

“…10,13,14 Whereas many studies have focused on the modulation of autophagy by apoptotic-signaling pathways, it is also clear that autophagy can regulate apoptosis. 4 In the present study, we have found that, post-TBI, moderate hypothermia could increase expression of autophagy and attenuate hippocampal cell death, which may suggest that the autophagy pathway may play an important role in the neuroprotective function of moderate hypothermia.…”

“…3 Macroautophagy (hereafter referred to as autophagy) is a catabolic process in which cells degrade their own components by enveloping them in double-membrane vesicles referred to as autophagosomes that are then targeted for lysosomal degradation. 4 Recently, a series of studies has reported the increase of autophagy in subarachnoid hemorrhage, intracerebral hemorrhage, hypoxia-ischemia, neurodegenerative disease, and TBI. [5][6][7][8][9][10] However, the function of autophagy in TBI remains controversial.…”

A role for c-FLIPL in the regulation of apoptosis, autophagy, and necroptosis in T lymphocytes

“…Autophagy supports cell survival in many circumstances; this cytoprotective role of autophagy is especially important upon nutrient withdrawal. 37 In T lymphocytes, autophagy is indispensible not only for surviving growth factor withdrawal, but also for regulating the mitochondria and endoplasmic reticulum. 31,38,39 How autophagy promotes cell survival in c-FLIP L À / À T cells remains to be determined.…”

Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia

“…30 Therefore, the expression levels of Bcl-2, Bcl-XL and Mcl-1 were investigated by western blot in CEM-R and CEM-S cells. Although we did not detect major differences between Bcl-2 and Mcl-1, Bcl-XL was expressed to a much higher extent in CEM-R when compared with CEM-S cells (Supplementary Figure S1).…”