Energetic adaptations: Metabolic control of endocytic membrane traffic

Abstract

Endocytic membrane traffic controls the access of myriad cell surface proteins to the extracellular milieu, and thus gates nutrient uptake, ion homeostasis, signaling, adhesion and migration. Coordination of the regulation of endocytic membrane traffic with a cell's metabolic needs represents an important facet of maintenance of homeostasis under variable conditions of nutrient availability and metabolic demand. Many studies have revealed intimate regulation of endocytic membrane traffic by metabolic cues, from the specific control of certain receptors or transporters, to broader adaptation or remodeling of the endocytic membrane network. We examine how metabolic sensors such as AMP‐activated protein kinase, mechanistic target of rapamycin complex 1 and hypoxia inducible factor 1 determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. We also examine how certain metabolites can directly control endocytic traffic proteins, such as the regulation of specific protein glycosylation by limiting levels of uridine diphosphate N‐acetylglucosamine (UDP‐GlcNAc) produced by the hexosamine biosynthetic pathway. From these ideas emerge a growing appreciation that endocytic membrane traffic is orchestrated by many intrinsic signals derived from cell metabolism, allowing alignment of the functions of cell surface proteins with cellular metabolic requirements. Endocytic membrane traffic determines how cells interact with their environment, thus defining many aspects of nutrient uptake and energy consumption. We examine how intrinsic signals that reflect metabolic status of a cell regulate endocytic traffic of specific proteins, and, in some cases, exert broad control of endocytic membrane traffic phenomena. Hence, endocytic traffic is versatile and adaptable and can be modulated to meet the changing metabolic requirements of a cell.

Endocytosis in the adaptation to cellular stress

“…In addition to phosphorylation, ubiquitination events play a critical role in regulating the uptake of specific cargo proteins. Moreover, recent data suggest that both endocytosed cargo proteins and endocytic factors such as AP180 and AAK1 (reviewed in [119]) can also be subject to modification by carbohydrates such as O-GlcNAc that may regulate endocytosis by so far unknown mechanisms. Aside from these post-translational mechanisms, the regulation of endocytosis at the transcriptional level including the possible role of alternative splicing is only now starting to be appreciated.…”

The multifaceted role of cell cycle regulators in the coordination of growth and metabolism

“…AMPK also phosphorylates proteins involved in the control of CME including, clathrin heavy chain, AP2 b2 subunit, dynamin 1, some other traffic coat proteins such as PTRF/cavin or Sec23/24, and several Rab proteins (reviewed in Ref. [92]). Interestingly, AMPK has been described as a target of cell cycle regulators.…”

AMP-activated protein kinase (AMPK) is required for recovery from metabolic stress induced by ultrasound microbubble treatment

“…USMB treatment leads to a reduction in ATP levels within the cell, and AMPK is required for restoring cellular ATP within 2 h following USMB treatment ( Figure 4 ). There are several mechanisms by which AMPK may promote metabolic adaptation resulting in replenishing of ATP levels (Herzig and Shaw, 2018; Rahmani et al, 2019). For instance, AMPK activation increases glucose uptake and promotes glycolysis, by acutely increasing the transport of glucose via facilitative glucose transporters such as GLUT1 (Wu et al, 2013) and phosphorylation of phosphofructokinase 2 (Marsin et al, 2000; Wu and Wei, 2012) as well as by transcriptional regulation of various glycolytic enzymes (Faubert et al, 2013; Marsin et al, 2000; Wu and Wei, 2012).…”