Publications by authors named "Michal Wasilewski"

Article Synopsis
  • - The presequence translocase TIM23 is crucial for transporting mitochondrial proteins into the matrix or inner membrane, with its core components being Tim23 and Tim17, but the details of the human TIM23 complex are not well understood.
  • - Both TIMM17A and TIMM17B, the human equivalents of Tim17, are regulated by the prohibitin complex, which is necessary for stabilizing these variants.
  • - The study highlights the role of OCIAD1 in working with prohibitins to protect the TIMM17A variant from degradation, suggesting an important regulatory relationship between OCIAD1, prohibitins, and the TIM23 complex.
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Mitochondria contain numerous proteins that utilize the chemistry of cysteine residues, which can be reversibly oxidized. These proteins are involved in mitochondrial biogenesis, protection against oxidative stress, metabolism, energy transduction to adenosine triphosphate, signaling and cell death among other functions. Many proteins located in the mitochondrial intermembrane space are imported by the mitochondrial import and assembly pathway the activity of which is based on the reversible oxidation of cysteine residues and oxidative trapping of substrates.

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Perturbed cellular protein homeostasis (proteostasis) and mitochondrial dysfunction play an important role in neurodegenerative diseases, however, the interplay between these two phenomena remains unclear. Mitochondrial dysfunction leads to a delay in mitochondrial protein import, causing accumulation of non-imported mitochondrial proteins in the cytosol and challenging proteostasis. Cells respond by increasing proteasome activity and molecular chaperones in yeast and C.

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Article Synopsis
  • - Mitochondria are crucial for cellular metabolism and maintain stability of mitochondrial DNA (mtDNA), which is vital for cell health and requires quick repair of any damage.
  • - Base excision repair (BER) is the main method for fixing DNA lesions, with Apurinic/Apyrimidinic Endonuclease 1 (APE1) being a key protein that processes damaged sites.
  • - This study found that oxidative stress triggers APE1 to quickly move from the mitochondrial intermembrane space to the matrix, and this movement is facilitated by the TIM23/PAM complex, suggesting the intermembrane space acts as a storage site for APE1.
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Synapses are the regions of the neuron that enable the transmission and propagation of action potentials on the cost of high energy consumption and elevated demand for mitochondrial ATP production. The rapid changes in local energetic requirements at dendritic spines imply the role of mitochondria in the maintenance of their homeostasis. Using global proteomic analysis supported with complementary experimental approaches, we show that an essential pool of mitochondrial proteins is locally produced at the synapse indicating that mitochondrial protein biogenesis takes place locally to maintain functional mitochondria in axons and dendrites.

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The mitochondrial cytochrome c oxidase, the terminal enzyme of the respiratory chain, contains heme and copper centers for electron transfer. The conserved COX2 subunit contains the Cu site, a binuclear copper center. The copper chaperones SCO1, SCO2, and COA6, are required for Cu center formation.

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Nuclear and mitochondrial genome mutations lead to various mitochondrial diseases, many of which affect the mitochondrial respiratory chain. The proteome of the intermembrane space (IMS) of mitochondria consists of several important assembly factors that participate in the biogenesis of mitochondrial respiratory chain complexes. The present study comprehensively analyzed a recently identified IMS protein cytochrome oxidase assembly factor 7 (COA7), or RESpiratory chain Assembly 1 (RESA1) factor that is associated with a rare form of mitochondrial leukoencephalopathy and complex IV deficiency.

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Mitochondria participate in plethora of vital processes in the cell such as energy production, other biochemical pathways and signaling. Over a thousand proteins co-operate to form the proteome of mitochondria. A great majority of mitochondrial precursor proteins are encoded in nuclear DNA and produced in the cytosol.

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Mitochondria are central power stations in the cell, which additionally serve as metabolic hubs for a plethora of anabolic and catabolic processes. The sustained function of mitochondria requires the precisely controlled biogenesis and expression coordination of proteins that originate from the nuclear and mitochondrial genomes. Accuracy of targeting, transport and assembly of mitochondrial proteins is also needed to avoid deleterious effects on protein homeostasis in the cell.

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The content of mitochondrial proteome is maintained through two highly dynamic processes, the influx of newly synthesized proteins from the cytosol and the protein degradation. Mitochondrial proteins are targeted to the intermembrane space by the mitochondrial intermembrane space assembly pathway that couples their import and oxidative folding. The folding trap was proposed to be a driving mechanism for the mitochondrial accumulation of these proteins.

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APE1 is a multifunctional protein with a fundamental role in repairing nuclear and mitochondrial DNA lesions caused by oxidative and alkylating agents. Unfortunately, comprehensions of the mechanisms regulating APE1 intracellular trafficking are still fragmentary and contrasting. Recent data demonstrate that APE1 interacts with the mitochondrial import and assembly protein Mia40 suggesting the involvement of a redox-assisted mechanism, dependent on the disulfide transfer system, to be responsible of APE1 trafficking into the mitochondria.

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Mitochondria are involved in many essential cellular activities. These broad functions explicate the need for the well-orchestrated biogenesis of mitochondrial proteins to avoid death and pathological consequences, both in unicellular and more complex organisms. Yeast as a model organism has been pivotal in identifying components and mechanisms that drive the transport and sorting of nuclear-encoded mitochondrial proteins.

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We describe the results of our research on population dynamics among brown hares reared in enclosures and then released into suitable natural habitat. Radio-tracking was used to follow the fate of 60 released brown hares over a 4-year period, extending between November 2005 and November 2009. The survival rate among these animals after 12 months was estimated to be 37 %, with 22 tagged individuals surviving beyond 1 year post-release.

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The mitochondrial protein AFG3L2 forms homo-oligomeric and hetero-oligomeric complexes with paraplegin in the inner mitochondrial membrane, named m-AAA proteases. These complexes are in charge of quality control of misfolded proteins and participate in the regulation of OPA1 proteolytic cleavage, required for mitochondrial fusion. Mutations in AFG3L2 cause spinocerebellar ataxia type 28 and a complex neurodegenerative syndrome of childhood.

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During human pregnancy, placental trophoblasts differentiate and syncytialize into syncytiotrophoblasts that sustain progesterone production [1]. This process is accompanied by mitochondrial fragmentation and cristae remodeling [2], two facets of mitochondrial apoptosis, whose molecular mechanisms and functional consequences on steroidogenesis are unclear. Here we show that the mitochondria-shaping protein Optic atrophy 1 (Opa1) controls efficiency of steroidogenesis.

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Mitochondria are key organelles in conversion of energy, regulation of cellular signaling and amplification of programmed cell death. The anatomy of the organelle matches this functional versatility in complexity and is modulated by the concerted action of proteins that impinge on its fusion-fission equilibrium. A growing body of evidence implicates changes in mitochondrial shape in the progression of apoptosis and, therefore, proteins governing such changes are likely candidates for involvement in pathogenetic mechanisms in neurodegeneration and cancer.

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The adenine nucleotide translocase (ANT), besides transferring ATP from the mitochondrial matrix to the rest of the cell, has also been proposed to be involved in mitochondrial permeability transition (MPT), and accordingly in mitochondrial Ca2+ homeostasis. In order to assess the role of ANT in Ca2+ signal transmission from the endoplasmic reticulum (ER) to mitochondria, we overexpressed the various ANT isoforms and measured the matrix [Ca2+] ([Ca2+]m) increases evoked by stimulation with IP3-dependent agonists. ANT overexpression reduced the amplitude of the [Ca2+]m peak following Ca2+ release, an effect that was markedly greater for ANT-1 and ANT-3 isoforms than for ANT-2.

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Long-chain N-acylethanolamines (NAEs) have been found to uncouple oxidative phosphorylation and to inhibit uncoupled respiration of rat heart mitochondria [Wasilewski, M., Wieckowski, M.R.

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Repeated, intermittent exposure to psychostimulants or stressors results in long-lasting, progressive sensitization of the behavioral effects of a subsequent amphetamine (AMPH) challenge. Although behavioral sensitization has also been observed following a single drug pretreatment, the sensitizing potential of a single exposure to stress is not clear. Both drug- and stress-induced sensitization depend on an enhanced dopaminergic neurotransmission in the mesolimbic DA system.

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Effects of N-acylethanolamines (NAEs): N-arachidonoylethanolamine (anandamide), N-oleoylethanolamine and N-palmitoylethanolamine, on energy coupling and permeability of rat heart mitochondria were investigated. In nominally Ca2+-free media, these compounds exerted a weak protonophoric effect manifested by dissipation of the transmembrane potential and stimulation of resting state respiration. The strongest action was exhibited by N-arachidonoylethanolamine, followed by N-oleoylethanolamine, whereas N-palmitoylethanolamine was almost inactive.

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