Biology subjects

Sliwinska, M. A.

Publications and source records attributed to Sliwinska, M. A..

5 recordsLinked to original sources

bioRxiv2025

Resolution of collided ribosomes by ZNF598 is required for adipocyte energy dissipation

Cellular adaptation to stress evoked by high energy demand requires tight coordination between transcriptional programs, protein synthesis, and organelle function. In many physiological contexts, metabolic remodeling depends on increased mitochondrial capacity and activity, placing high demands on the translational machinery. Beige and brown adipocytes, which undergo rapid mitochondrial expansion and activation in response to physiological cues, provide a powerful model to study how cells adapt their translational output to meet increased metabolic demand. How translational fidelity is maintained, and stress-associated conflicts in protein synthesis are resolved during such adaptive processes, remains incompletely understood. Here, we identify ZNF598 as a key factor that resolves translation stress caused by ribosome collisions during metabolic adaptation of adipocytes. We show that diverse physiological stimuli, including hormonal signaling, environmental challenges, and dietary changes, induce ZNF598 and associated enzymes in metabolically active cells. ZNF598 is required for efficient mitochondrial biogenesis and function, supporting adaptive increases in respiration and energy expenditure. Loss of ZNF598 compromises these adaptive responses and leads to metabolic dysfunction, whereas enhancement of ZNF598 activity improves cellular and organismal metabolic flexibility. Together, these findings indicate that distal steps of the translational machinery are a rate-limiting factor for adaptation to increased energy demand.

cell biology↗

bioRxiv2024

Projections from thalamic nucleus reuniens to hippocampal CA1 area enable context value updating

The ability to extinguish contextual fear in a changing environment is crucial for animal survival. Recent data support the role of the thalamic nucleus reuniens (RE) and its projections to the dorsal hippocampal CA1 area (RE[->]dCA1) in this process. However, it remains poorly understood how RE impacts dCA1 neurons during contextual fear extinction (CFE). Here, we reveal that the RE[->]dCA1 pathway contributes to extinction of contextual fear by affecting CFE-induced molecular remodeling of excitatory synapses. Anatomical tracing and chemogenetic manipulation in mice demonstrate that RE neurons form synapses and regulate synaptic transmission in the stratum oriens (SO) and lacunosum-moleculare (SLM) of the dCA1 area, but not in the stratum radiatum (SR). We also observe CFE-specific structural changes of excitatory synapses and expression of the synaptic scaffold protein, PSD-95, in both strata innervated by RE, but not in SR. Interestingly, only the changes in SLM are specific for the dendrites innervated by RE. To further support the role of the RE[->]dCA1 projection in CFE, we demonstrate that brief chemogenetic inhibition of the RE[->]dCA1 pathway during a CFE session persistently impairs the formation of CFE memory and CFE-induced changes of PSD-95 levels in SLM. Thus, our data indicate that RE participates in CFE by regulating CFE-induced molecular remodeling of dCA1 synapses.

animal behavior and cognition↗

bioRxiv2023

Molecular mechanisms of heavy metal adaptation of an extremophilic red alga Cyanidioschyzon merolae

The order of Cyanidiales comprise seven acido-thermophilic red microalgal species thriving in hot springs of volcanic origin characterized by extremely low pH, moderately high temperatures and the presence of elevated concentrations of sulphites and heavy metals that are prohibitive for most other organisms. Little is known about the molecular mechanisms of Cyanidiales long-term adaptation to such hostile environments, in particular to heavy metals, yet elucidation of these processes is important for understanding the evolution of the metabolic pathways underlying heavy metal detoxification for developing rational strategies for heavy metal bioremediation. Here, we investigated the long-term adaptive responses of Cyanidioschyzon merolae cells, a member of Cyanidiales, to extremely high nickel concentrations. Through complementary approaches based on physiological, microscopic and elemental analyses we dissect several molecular mechanisms underlying the long-term adaptation of this model extremophilic microalga to high Ni exposure. These include: (i) extrusion of Ni from the cells and lack of significant Ni accumulation inside the cells; (ii) maintenance of efficient photoprotective responses including non-photochemical quenching and state transitions; (iii) dynamic remodeling of the chloroplast ultrastructure such as formation of metabolically active prolamellar bodies and plastoglobuli together with loosening of the thylakoid membranes; (iv) activation of ROS amelioration metabolic pathways; and (v) preservation of the efficient respiratory chain functionality. All the dynamically regulated processes identified in this study underlie the remarkable adaptability of C. merolae to extremely high Ni levels that exceed by several orders of magnitude the levels of this heavy metal found in the natural environment of this extremophile.

cell biology↗

bioRxiv2023

Phosphorylation of PSD-95 at Serine 73 in dCA1 is required for extinction of contextual fear

The updating of contextual memories is essential for survival in a changing environment. Accumulating data indicate that the dorsal CA1 area (dCA1) contributes to this process. However, the cellular and molecular mechanisms of contextual fear memory updating remain poorly understood. Postsynaptic density protein 95 (PSD-95) regulates the structure and function of glutamatergic synapses. Here, using dCA1-targeted genetic manipulations in vivo, combined with ex vivo 3D electron microscopy and electrophysiology, we identify a novel, synaptic mechanism that is induced during attenuation of contextual fear memories and involves phosphorylation of PSD-95 at Serine 73 in dCA1. Our data provide the proof that PSD-95-dependent synaptic plasticity in dCA1 is required for updating of contextual fear memory.

neuroscience↗

bioRxiv2020

PSD-95 in dorsal CA1 contributes to the persistence of fear memory

The ability to extinguish fearful memories is essential for survival. Accumulating data indicate that the dorsal CA1 area (dCA1) contributes to this process. However, the cellular and molecular basis of fear memory extinction remains poorly understood. Postsynaptic density protein 95 (PSD-95) regulates the structure and function of glutamatergic synapses. Here, using dCA1-targeted genetic and chemogenetic manipulations in vivo combined with PSD-95 immunostaining and 3D electron microscopy ex vivo, we demonstrate that phosphorylation of PSD-95 at serine 73 PSD-95(S73) is necessary for contextual fear extinction-induced expression of PSD-95 and synaptic plasticity. Moreover, PSD-95(S73) phosphorylation is not necessary for fear memory formation and recall but is required for extinction of contextual fear. Overall, our data shows how PSD-95-dependent synaptic plasticity in the hippocampus contributes to the persistence of fear memories.

neuroscience↗