The role of ion homeostasis imbalance due to citrate accumulation in fluoroacetic acid (FAA) in crassa

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Raquel Bernardino (Author) ICBAS

Journal

The Journal is awaiting validation by the Administrative Services.

Title: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY

Vol. 271

ISSN: 1532-0456

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00Y-GDN

DOI: 10.1016/j.cbpc.2023.109661

Abstract (EN): Fluoroacetic acid (FAA) is a poison commonly used for the lethal control of invasive species in Australia and New Zealand. Despite its widespread use and long history as a pesticide, no effective treatment for accidental poisoning exists. Although it is known to inhibit the tricarboxylic acid (TCA) cycle, specific details of FAA toxicology have remained elusive, with hypocalcemia suggested to be involved in the neurological symptoms prior to death. Here, we study the effects of FAA on cell growth and mitochondrial function using the filamentous fungi Neurospora crassa as model organism. FAA toxicosis in N. crassa is characterized by an initial hyperpo-larization and subsequent depolarization of the mitochondrial membranes, followed by a significant intracellular decrease in ATP and increase in Ca2+. The development of mycelium was markedly affected within 6 h, and growth impaired after 24 h of FAA exposure. Although the activity of mitochondrial complexes I, II and IV was impaired, the activity of citrate synthase was not affected. Supplementation with Ca2+ exacerbated the effects of FAA in cell growth and membrane potential. Our findings suggest that an imbalance created in the ratio of ions within the mitochondria may lead to conformational changes in ATP synthase dimers due to mitochondrial Ca2+ uptake, that ultimately result in the opening of the mitochondrial permeability transition pore (MPTP), a decrease in membrane potential, and cell death. Our findings suggest new approaches for the treatment research, as well as the possibility to use N. crassa as a high-throughput screening assay to evaluate a large number of FAA antidote candidates.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11