Mechanisms of Autophagy in Metabolic Stress Response

Gross, Angelina S.; Graef, Martin

doi:10.1016/j.jmb.2019.09.005

Cited by 58 publications

(37 citation statements)

References 267 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Autophagy is the process in which cells coat their damaged organelles or proteins in a double membrane structure and transport them to the lysosomes for degradation 9 . Autophagy is a dynamic biological process that is very important in the growth, development and differentiation of the cells [10][11][12] . However, excessive autophagy results in the accumulation of abnormal proteins in the cells that block the normal activities of the cells.…”

Section: Introductionmentioning

confidence: 99%

Gelatine nanostructured lipid carrier encapsulated FGF15 inhibits autophagy and improves recovery in spinal cord injury

et al. 2020

View full text Add to dashboard Cite

Gelatine nanostructured lipid carriers (GNLs) have attracted increasing attention due to their biodegradable status and capacity to capture various biologically active compounds. Many studies demonstrated that fibroblast growth factor therapies after spinal cord injury (SCI) can be used in the future for the recovery of neurons. In this study, the therapeutic effects of GNL-encapsulated fibroblast growth factor 15 (FGF15) and FGF15 were compared in SCI. The FGF15-GNLs had 88.17 ± 1.22% encapsulation efficiency and 4.82 ± 0.12% loading capacity. The effects of FGF15-GNLs and FGF15 were assessed based on the Basso–Beattie–Bresnahan (BBB) locomotion scale, inclined plane test and footprint analysis. Immunofluorescent staining was used to identify the expression of autophagy-associated proteins, GFAP (glial fibrillary acidic protein) and neurofilament 200 (NF200). FGF15-GNLs use enhanced the repair after SCI compared to the effect of FGF15. The suppression of autophagy-associated proteins LC3-II and beclin-1, and p62 enhancement by FGF15-GNLs treatment were more pronounced. Thus, the effects of FGF15-GNLs on the recovery after SCI are related to the inhibition of autophagy and glial scar, and promotion of nerve regeneration in SCI.

show abstract

Section: Introductionmentioning

confidence: 99%

Gelatine nanostructured lipid carrier encapsulated FGF15 inhibits autophagy and improves recovery in spinal cord injury

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Autophagy catabolizes damaged cellular components to protect cells against stress and maintain homeostasis (125,126). There are three types of autophagy: microautophagy in which damaged cellular components are directly sequestered by the lysosomes for degradation, Chaperone-mediated autophagy in which specific motif-containing cargo proteins are delivered to the lysosome by chaperone complexes, and macroautophagy in which damaged cytosolic components, including organelles, are sequestered into double-membrane autophagosomes that fuse with the lysosome.…”

Section: Autophagy Aging and Mptpmentioning

confidence: 99%

The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity

Rottenberg¹,

Hoek²

2020

Preprint

View full text Add to dashboard Cite

The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

show abstract

“…Generally, cells exhibit a low and basal level of autophagy. But the level of autophagy can significantly increase in response to external environment stress, including mechanical stress and nutrient deprivation, in order to provide nutrients for essential cellular functions (Gross and Graef, 2019). The HO-1, which has been identified in many tissues and organs as well as different pathophysiological scenarios, is the rate-limiting enzyme in the metabolism of heme into biliverdin, carbon monoxide and iron, and can exert cytoprotective effects against various external environment stress-induced oxidative stress, inflammation and cell death (Otterbein et al, 2016;Chiang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Moderate Fluid Shear Stress Regulates Heme Oxygenase-1 Expression to Promote Autophagy and ECM Homeostasis in the Nucleus Pulposus Cells

Chen

Qin

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

In vertebrate, the nucleus pulposus (NP), which is an essential component of the intervertebral disk, is constantly impacted by fluid shear stress (FSS); however, molecular mechanism(s) through which FSS modulates the NP homeostasis is poorly understood. Here we show that FSS regulates the extracellular matrix (ECM) homeostasis in NP cells. A moderate dose of FSS (i.e., 12 dyne/cm 2) increases the sulfated glycosaminoglycan (sGAG) content and protein levels of Col2a1 and Aggrecan and decreases those of matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motif 5 (ADMATS5) in rat NP cells, while a higher dose of FSS (i.e., 24 dyne/cm 2) displays opposite effects. Results from RNA sequencing analysis, quantitative real-time RT-PCR analysis and western blotting establish that the heme oxygenase-1 (HO-1) is a key downstream mediator of the FSS actions in NP cells. HO-1 knockdown abolishes FSS-induced alterations in ECM protein production and sGAG content in NP cells, which is reversed by HO-1 induction. Furthermore, FSS activates the autophagic pathway by increasing the LC3-II/LC3-I ratio, Beclin-1 protein level, and formation of autophagosome and autolysosome and thereby regulates ECM protein and sGAG production in a HO-1 dependent manner. Finally, we demonstrate that the intraflagellar transport (IFT) 88, a core trafficking protein of primary cilia, is critically involved in the HO-1-mediated autophagy activation and ECM protein and sGAG production in FSS-treated NP cells. Thus, we for the first time demonstrate that FSS plays an important role in maintaining ECM homeostasis through HO-1-dependent activation of autophagy in NP cells.

show abstract

Mechanisms of Autophagy in Metabolic Stress Response

Cited by 58 publications

References 267 publications

Gelatine nanostructured lipid carrier encapsulated FGF15 inhibits autophagy and improves recovery in spinal cord injury

Gelatine nanostructured lipid carrier encapsulated FGF15 inhibits autophagy and improves recovery in spinal cord injury

The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity

Moderate Fluid Shear Stress Regulates Heme Oxygenase-1 Expression to Promote Autophagy and ECM Homeostasis in the Nucleus Pulposus Cells

Contact Info

Product

Resources

About