Endocytosis in the adaptation to cellular stress

Abstract

Cellular life is challenged by a multitude of stress conditions, triggered for example by alterations in osmolarity, oxygen or nutrient supply. Hence, cells have developed sophisticated stress responses to cope with these challenges. Some of these stress programs such as the heat shock response are understood in great detail, while other aspects remain largely elusive including potential stress-dependent adaptations of the plasma membrane proteome. The plasma membrane is not only the first point of encounter for many types of environmental stress, but given the diversity of receptor proteins and their associated molecules also represents the site at which many cellular signal cascades originate. Since these signaling pathways affect virtually all aspects of cellular life, changes in the plasma membrane proteome appear ideally suited to contribute to the cellular adaptation to stress. The most rapid means to alter the cell surface proteome in response to stress is by alterations in endocytosis. Changes in the overall endocytic flux or in the endocytic regulation of select proteins conceivably can help to counteract adverse environmental conditions. In this review we summarize recent data regarding stress-induced changes in endocytosis and discuss how these changes might contribute to the cellular adaptation to stress in different systems. Future studies will be needed to uncover the underlying mechanisms in detail and to arrive at a coherent picture.

Unconventional endocytosis and trafficking of transferrin receptor induced by iron

“…Indeed, it has been shown that HIF2α is inhibited by ferrous iron (Schwartz et al, 2019) and expo-sure to FAC may end up in an increased content of ferrous iron thanks to reductases that may assist iron transporters like DMT1 or members of the ZIP family. However, it has been suggested that endocytosis is facilitated by hypoxia and hence elevated HIF activity (reviewed in López-Hernández et al, 2020). This mechanism, therefore, does not seem to apply to the situation described in the present study.…”

Dictyostelium Differentiation-Inducing Factor-1 Promotes Glucose Uptake, at Least in Part, via an AMPK-Dependent Pathway in Mouse 3T3-L1 Cells

“…By uncoupling mitochondrial activities, DIF may disturb ATP production and activate AMPK, which may then induce GLUT1 translocation to the plasma membrane and glucose uptake. It is generally unknown how AMPK activation induces GLUT1 translocation, whereas AMPK activation may inhibit GLUT1 internalization (endocytosis) to promote glucose uptake by triggering the degradation of TXNIP (thioredoxin-interacting protein), a stimulator of GLUT1 endocytosis [ 49 , 50 ]. Note that DIF may induce GLUT1 translocation partly via an AMPK-independent pathway, but it remains to be elucidated how DIF induces GLUT1 translocation.…”

Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization

“…It is reasonable to suppose that inhibition of this pathway by CME inhibitors, on one hand, and saturation of clathrin-independent endocytic pathways by exposure to PEG-SO-MNPs, on the other hand, could compromise cellular homeostasis and result in cellular stress. A close relation between endocytosis and cellular stress has been highlighted in several publications [ 63 ]. We can hypothesize that under such conditions either different endocytic pathways, for example, macropinocytosis as suggested by Rothen-Rutishauser et al [ 50 ] or non-selective alternative endocytic structures, discussed by Boucrot et al [ 64 ] or Vega et al [ 65 ], could be upregulated to provide compensatory endocytic pathways.…”