Biology subjects

Brunetti, D.

Publications and source records attributed to Brunetti, D..

3 recordsLinked to original sources

bioRxiv2026

Impacts of vessel noise on red drum (Sciaenops ocellatus) spawning choruses in Saint Andrew Bay, Florida, U.S.A.

Noise pollution is an increasing threat to soniferous fishes, however, research on noise pollution impacts is limited to few species and rarely studied in situ. Red Drum (Sciaenops ocellatus) is an estuarine, fishery species that choruses during spawning. We tested predictions of the hypothesis that Red Drum alter sound production in response to vessel noise. We used passive acoustic monitoring in 2021 and 2022 at an estuarine inlet and Generalized Least Squares (GLS) models to assess vessel sound exposure levels over time (SEL) and other abiotic parameters on Red Drum chorus SELs. GLS models of daily crepuscular choruses indicated a >5% reduction in proportion to crepuscular vessel noise in 2021. GLS models testing influence of abiotic variables and prior vessel noise, predicted reduced chorus SELs proportional to prior noise SEL: ca. 5% and 3% of vessel SEL in 2021 and 2022, respectively. In some instances, SEL during vessel noise was lower than fish chorus SEL immediately prior, indicating instances when fish reduced chorus amplitude during vessel noise or fled the immediate area. In cases when SEL of vessel noise periods exceeded fish calling SEL immediately prior, it is not known if fish modulated calling amplitude because the portion of combined vessel noise and fish chorus amplitude from vessels is unknown. In peak spawning season (September-October) vessel noise was frequent, detected in >31% of recordings in both years and up to 100% of recordings on some dates. Observations of disrupted choruses and high vessel noise prevalence suggest spawning behavior may be impacted by abundant vessel noise.

animal behavior and cognition↗

bioRxiv2024

The mitochondrial unfolded protein response promotes senescence in human microglia by increasing S-adenosylmethionine availability for polyamine synthesis.

Mitochondria have evolved a specialized mitochondrial unfolded protein response (UPRmt) to maintain proteostasis and promote recovery under stress. Studies in simple organisms have shown that UPRmt activation in glial cells supports proteostasis through beneficial noncell-autonomous communication with neurons. However, the role of mitochondrial stress responses in the human brain remains unclear. To address this gap, we investigated the cell type-specific effects of mitochondrial proteotoxic stress using human induced pluripotent stem cell-derived neuronal and glial cultures, as well as brain organoids. We show that mitochondrial proteotoxic stress induces metabolic rewiring in human microglia, marked by depletion of S-adenosylmethionine and lipid remodeling, ultimately leading to a senescent phenotype. Using human neuronal-glial tricultures and microglia-containing brain organoids, we identified the specific contributions of microglia to brain senescence and mitochondrial stress-driven neurodegenerative processes. UPRmt activation disrupts microglial communication with neighboring cells, triggering inflammatory signaling and impairing proteostasis. Together, these findings reveal how impaired mitochondrial proteostasis alters intercellular networks and identify a critical role for the UPRmt in neurodegenerative disease pathogenesis.

neuroscience↗

bioRxiv2020

Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids

Mutations in pitrilysin metallopeptidase 1 (PITRM1), a mitochondrial protease involved in mitochondrial precursor processing and degradation, result in a slow-progressive syndrome, characterized by cerebellar ataxia, psychotic episodes and obsessive behavior as well as cognitive decline. To investigate the pathogenetic mechanisms of mitochondrial presequence processing, we employed cortical neurons and cerebral organoids generated from PITRM1 knockout human induced pluripotent stem cells (iPSCs). PITRM1 deficiency strongly induced mitochondrial unfolded protein response (UPRmt) and enhanced mitochondrial clearance in iPSC-derived neurons. Furthermore, we observed increased levels of amyloid precursor protein and amyloid {beta} in PITRM1 knockout neurons. However, neither cell death nor protein aggregates were observed in 2D iPSC-derived cortical neuronal cultures. On the contrary, cerebral organoids generated from PITRM1 knockout iPSCs spontaneously developed over time pathological features of Alzheimers disease (AD), including accumulation of protein aggregates, tau pathology, and neuronal cell death. Importantly, we provide evidence for a protective role of UPRmt and mitochondrial clearance against impaired mitochondrial presequence processing and proteotoxic stress. In summary, we propose a novel concept of PITRM1-linked neurological syndrome whereby defects of mitochondrial presequence processing induce an early activation of UPRmt that, in turn, modulates cytosolic quality control pathways. Thus our work supports a mechanistic link between mitochondrial function and common neurodegenerative proteinopathies.

neuroscience↗