The ERK1/2-ATG13-FIP200 signaling cascade is required for autophagy induction to protect renal cells from hypoglycemia-induced cell death.
J Cell Physiol
; 236(10): 6932-6947, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-33682133
ABSTRACT
Autophagy, an evolutionarily conserved lysosomal degradation pathway, is known to regulate a variety of physiological and pathological processes. At present, the function and the precise mechanism of autophagy regulation in kidney and renal cells remain elusive. Here, we explored the role of ERK1 and ERK2 (referred as ERK1/2 hereafter) in autophagy regulation in renal cells in response to hypoglycemia. Glucose starvation potently and transiently activated ERK1/2 in renal cells, and this was concomitant with an increase in autophagic flux. Perturbing ERK1/2 activation by treatment with inhibitors of RAF or MEK1/2, via the expression of a dominant-negative mutant form of MEK1/2 or RAS, blocked hypoglycemia-mediated ERK1/2 activation and autophagy induction in renal cells. Glucose starvation also induced the accumulation of reactive oxygen species in renal cells, which was involved in the activation of the ERK1/2 cascade and the induction of autophagy in renal cells. Interestingly, ATG13 and FIP200, the members of the ULK1 complex, contain the ERK consensus phosphorylation sites, and glucose starvation induced an association between ATG13 or FIP200 and ERK1/2. Moreover, the expression of the phospho-defective mutants of ATG13 and FIP200 in renal cells blocked glucose starvation-induced autophagy and rendered cells more susceptible to hypoglycemia-induced cell death. However, the expression of the phospho-mimic mutants of ATG13 and FIP200 induced autophagy and protected renal cells from hypoglycemia-induced cell death. Taken together, our results demonstrate that hypoglycemia activates the ERK1/2 signaling to regulate ATG13 and FIP200, thereby stimulating autophagy to protect the renal cells from hypoglycemia-induced cell death.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Proteína Quinasa 1 Activada por Mitógenos
/
Proteína Quinasa 3 Activada por Mitógenos
/
Proteínas Relacionadas con la Autofagia
/
Glucosa
/
Hipoglucemia
/
Riñón
Límite:
Humans
Idioma:
En
Revista:
J Cell Physiol
Año:
2021
Tipo del documento:
Article
País de afiliación:
China