ApoE4 (Δ272-299) induces mitochondrial-associated membrane formation and mitochondrial impairment by enhancing GRP75-modulated mitochondrial calcium overload in neuron.

ABSTRACT:

Background

Apolipoprotein E4 (apoE4) is a major genetic risk factor of Alzheimer's disease. Its C-terminal-truncated apoE4 (Δ272-299) has neurotoxicity by affecting mitochondrial respiratory function. However, the molecular mechanism(s) underlying the action of apoE4 (Δ272-299) in mitochondrial function remain poorly understood.

Methods

The impact of neuronal apoE4 (Δ272-299) expression on ER stress, mitochondrial-associated membrane (MAM) formation, GRP75, calcium transport and mitochondrial impairment was determined in vivo and in vitro. Furthermore, the importance of ER stress or GRP75 activity in the apoE4 (Δ272-299)-promoted mitochondrial dysfunction in neuron was investigated.

Results

Neuronal apoE4 (Δ272-299) expression induced mitochondrial impairment by induc

SUBMITTER: Liang T 

PROVIDER: S-EPMC7937300 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature