Inhibiting mtDNA transcript translation alters Alzheimer's disease-associated biology.

ABSTRACT:

Introduction

Alzheimer's disease (AD) features changes in mitochondrial structure and function. Investigators debate where to position mitochondrial pathology within the chronology and context of other AD features.

Methods

To address whether mitochondrial dysfunction alters AD-implicated genes and proteins, we treated SH-SY5Y cells and induced pluripotent stem cell (iPSC)-derived neurons with chloramphenicol, an antibiotic that inhibits mtDNA-generated transcript translation. We characterized adaptive, AD-associated gene, and AD-associated protein responses.

Results

SH-SY5Y cells and iPSC neurons responded to mtDNA transcript translation inhibition by increasing mtDNA copy number and transcription. Nuclear-expressed respiratory chain mRNA and protein levels also chang

SUBMITTER: Gabrielli AP 

PROVIDER: S-EPMC11667520 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature