Source: europepmc · Mandel AR. · Research Square · 2026-05-25
URL: https://europepmc.org/article/PPR/PPR1237947
AI rationale (4/5, tier: preliminary): Mechanism-focused transcriptomic study of ERRα/γ-regulated mitochondrial stress responses in neuronal cells; directly addresses mitochondrial biogenesis regulators and UPRmt pathways.
<title>Abstract</title> <p>Mitochondrial dysfunction is implicated in neurodegenerative and neuropsychiatric disorders, yet the transcriptional mechanisms governing mitochondrial stress-response pathways remain incompletely understood. I investigated whether mitochondrial and stress-response genes exhibit coordinated or heterogeneous expression patterns in neuronal-like cells following disruption of mitochondrial regulatory pathways. Using targeted transcriptomic analysis, I assessed gene expression changes in SH-SY5Y cells following siRNA-mediated depletion of estrogen-related receptors ERRα and ERRγ. Log2 fold changes were calculated from TPM data for genes involved in electron transport, mitochondrial translation, metabolism, redox regulation, mitophagy, and stress signaling. Both ERRα and ERRγ depletion produced heterogeneous transcriptional responses with concurrent upregulation and downregulation observed across all functional categories. Core mitochondrial genes including electron transport chain components and mitochondrial ribosomal proteins exhibited divergent regulation. Redox- and ferroptosis-related genes also showed mixed responses, while mitophagy-associated genes were consistently upregulated, suggesting activation of mitochondrial quality control pathways. ERRγ depletion induced a more pronounced transcriptional response including stronger upregulation of stress signaling genes and greater downregulation of select redox-related targets. These findings indicate that mitochondrial regulatory disruption elicits a heterogeneous, multi-pathway response, reflecting competing compensatory and pathological processes in neuronal systems.</p>