Low-Dose Microcystin-LR Elicits Sex-Dimorphic Transcriptomic Responses in Senescent Nothobranchius furzeri

Verdict. Here, we used the naturally short-lived turquoise killifish, Nothobranchius furzeri, to investigate transcriptional responses to low-level MC-LR exposure in a senescent vertebrate. It intersects mitochondrial stress/dysfunction themes (aging; systemic metabolic stress).

What the authors report

Microcystin-LR (MC-LR), a cyanobacterial toxin produced during harmful algal blooms, is an increasing environmental and public health concern as the frequency and intensity of harmful algal blooms continue to rise globally. While the effects of MC-LR have been extensively studied in young organisms, much less is known about how aging influences susceptibility to cyanotoxin exposure.

Key results stated in the abstract include the following. Here, we used the naturally short-lived turquoise killifish, Nothobranchius furzeri, to investigate transcriptional responses to low-level MC-LR exposure in a senescent vertebrate. Among the shared responses, pck1, a key regulator of gluconeogenesis, was strongly downregulated in both sexes, accompanied by altered expression of genes associated with mitochondrial function, metabolic regulation, extracellular matrix remodeling, and genome maintenance. Our study identifies biological sex as an important determinant of cyanotoxin responses in an aging context and establishes naturally aged N. furzeri as a tractable vertebrate model for investigating interactions between environmental exposure and biological aging.

Why it matters for mitochondrial biology

Within mitochondrial research, this work maps primarily to metabolism, immunology, aging, structural biology. It is relevant to mitochondrial dysfunction discourse because the abstract invokes aging, systemic metabolic stress. That does not by itself establish a validated disease mechanism; it indicates thematic proximity. Server: biorxiv. Posted 2026-08-21. Synthesis confidence is bounded by abstract completeness.

Study design (abstract-level)

Approximately 8-month-old GRZ killifish were exposed to a low dose of 0.5 μg/L MC-LR, followed by whole-body RNA sequencing and sex-stratified differential expression analysis. Among the shared responses, pck1, a key regulator of gluconeogenesis, was strongly downregulated in both sexes, accompanied by altered expression of genes associated with mitochondrial function, metabolic regulation, extracellular matrix remodeling, and genome maintenance. Males exhibited prominent remodeling of skeletal muscle and contractile programs, supported by enrichment of sarcomeric, myofilament, and contractile-fiber-associated genes.

Principal findings

1. Here, we used the naturally short-lived turquoise killifish, Nothobranchius furzeri, to investigate transcriptional responses to low-level MC-LR exposure in a senescent vertebrate.
2. Among the shared responses, pck1, a key regulator of gluconeogenesis, was strongly downregulated in both sexes, accompanied by altered expression of genes associated with mitochondrial function, metabolic regulation, extracellular matrix remodeling, and genome maintenance.
3. Our study identifies biological sex as an important determinant of cyanotoxin responses in an aging context and establishes naturally aged N. furzeri as a tractable vertebrate model for investigating interactions between environmental exposure and biological aging.

Limitations of this brief

• This Mitos brief is an abstract-level synthesis of a preprint; it is not peer review and not a substitute for reading the full paper.
• Preprint status: findings may change with revision or journal review.
• Effect sizes, n numbers, statistics, and full experimental controls are typically incomplete at abstract resolution.
• Comparator/control language is weak or absent in the abstract, limiting causal inference from this brief alone.
• Primary source: biorxiv DOI 10.64898/2026.08.17.745368 (posted 2026-08-21).

Open scientific questions

• Which specific experimental panels in the full paper establish the strongest causal claim, and how robust are the controls?
• How do these findings sit relative to prior literature on the same pathway—replication, contradiction, or incremental extension?

Bottom line

For mitochondrial biologists focused on metabolism, immunology, aging, this preprint is worth full-text review if the topic matches your program. Abstract-level takeaway: Here, we used the naturally short-lived turquoise killifish, Nothobranchius furzeri, to investigate transcriptional responses to low-level MC-LR exposure in a senescent vertebrate. Confirm methods, effect sizes, and controls in the full PDF before citing the result as established.

Bibliographic record

Abstract-based editorial synthesis by Mitos. Not peer review.