Glucose-Induced Regulation of Protein Import Receptor Tom22 by Cytosolic and Mitochondria-Bound Kinases

SummaryMost mitochondrial proteins are imported by the translocase of the outer mitochondrial membrane (TOM). Tom22 functions as central receptor and transfers preproteins to the import pore. Casein kinase 2 (CK2) constitutively phosphorylates the cytosolic precursor of Tom22 at Ser44 and Ser46 and, thus, promotes its import. It is unknown whether Tom22 is regulated under different metabolic conditions. We report that CK1, which is involved in glucose-induced signal transduction, is bound to mitochondria. CK1 phosphorylates Tom22 at Thr57 and stimulates the assembly of Tom22 and Tom20. In contrast, protein kinase A (PKA), which is also activated by the addition of glucose, phosphorylates the precursor of Tom22 at Thr76 and impairs its import. Thus, PKA functions in an opposite manner to CK1 and CK2. Our results reveal that three kinases regulate the import and assembly of Tom22, demonstrating that the central receptor is a major target for the posttranslational regulation of mitochondrial protein import

Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family

Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation

AAA Proteases: Guardians of Mitochondrial Function and Homeostasis

Mitochondria are dynamic, semi-autonomous organelles that execute numerous life-sustaining tasks in eukaryotic cells. Functioning of mitochondria depends on the adequate action of versatile proteinaceous machineries. Fine-tuning of mitochondrial activity in response to cellular needs involves continuous remodeling of organellar proteome. This process not only includes modulation of various biogenetic pathways, but also the removal of superfluous proteins by adenosine triphosphate (ATP)-driven proteolytic machineries. Accordingly, all mitochondrial sub-compartments are under persistent surveillance of ATP-dependent proteases. Particularly important are highly conserved two inner mitochondrial membrane-bound metalloproteases known as m-AAA and i-AAA (ATPases associated with diverse cellular activities), whose mis-functioning may lead to impaired organellar function and consequently to development of severe diseases. Herein, we discuss the current knowledge of yeast, mammalian, and plant AAA proteases and their implications in mitochondrial function and homeostasis maintenance

Impact of a death anxiety on self control mechanisms

Prezentowane badania miały na celu sprawdzenie czy lęk przed śmiercią wywiera wpływ na mechanizmy samokontroli. Na podstawie przeprowadzonego przeglądu literatury przyjęto założenie, że lęk przed śmiercią istotnie wpływa na samokontrole osłabiając jej działanie. Część teoretyczna pracy w pierwszej kolejności poświęcona jest charakterystyce funkcji wykonawczych, a następnie szczegółowemu opisowi mechanizmów samokontroli. Dalej przedstawiona jest krótka charakterystyka emocji oraz zjawiska lęku, ze szczególnym uwzględnieniem lęku przed śmiercią. Kończy ją opis mechanizmów obronnych, jako struktur nieodłącznie związanych z lękiem. W celu uzyskania odpowiedzi na postawione pytanie badawcze grupę badawczą podzielono na eksperymentalną (N=32) i kontrolną (N=30) i poddano badaniu kwestionariuszowemu w postaci zestawu trzech kwestionariuszy. Zestawy dla grupy kontrolnej i eksperymentalnej różniły się między sobą tylko kolejnością, która była formą manipulacji eksperymentalnej. Zastosowano Kwestionariusz Lęku jako Cechy i Lęku jako Stanu STAI (Spielberger, Strelau, Wrześniewski, Tysarczyk), Kwestionariusz Samokontroli – Nowy Arkusz Samowiedzy (Nęcka i in.), oraz Kwestionariusz Lęku i Fascynacji Śmiercią – Skala Lęku przed śmiercią (Żmojtel-Piotrowska, Piotrowski). W grupie eksperymentalnej kwestionariusze związane z lękiem wypełniane były na początku, natomiast w grupie kontrolnej - na końcu zestawu. Następnie porównano wyniki obu grup na skali Kwestionariusza Samokontroli, aby zweryfikować hipotezę badawczą. Wyniki okazały się nieistotne statystycznie. W interpretacji wyników wskazane zostały czynniki, które nie zostały uwzględnione w badaniu, a które mogły mieć wpływ na jego przebieg.The topic of the presented study was how an death anxiety influenses on a self control mechanisms. A theoretical introduction of this study includes characteristic of the executive functions, especially of the self control. Then there is a description of emotions. It is focused on the anxiety and a very specific kind of anxiety which is a death anxiety. In the end of the theory part there is a depiction of the defence mechanisms, which are connected with the death anxiety. The State–Trait Anxiety Inventory, NAS-50: scale for the assessment of self-control and Death Anxiety and Fascination Scale were selected as measures. There were two groups: control and experimental. In an experimental group the questionnaires connected with the anxiety were in the beginning, whereas in control group they were in the end. The results were not statistically significant

Mitochondrial protein import under kinase surveillance

Despite the simplicity of the yeast Saccharomyces cerevisiae,its basic cellular machinery tremendously mirrors that of higher eukaryotic counterparts. Thus, this unicellular organism turned out to be an invaluable model system to study the countless mechanisms that govern life of the cell. Recently, it has also enabled the deciphering of signalling pathways that control flux of mitochondrial proteins to the organelle according to metabolic requirements. For decades mitochondria were considered autonomous organelles that are only partially incorporated into cellular signalling networks. Consequently, only little has been known about the role of reversible phosphorylation as a meaningful mechanism that orchestrates mitochondrial biology accordingly to cellular needs. Therefore, research in this direction has been vastly neglected. However, findings over the past few years have changed this view and new exciting fields in mitochondrial biology have emerged. Here, we summarize recent discoveries in the yeast model system that point towards a vital role of reversible phosphorylation in regulation of mitochondrial protein import

AAA Proteases: Guardians of Mitochondrial Function and Homeostasis

Mitochondria are dynamic, semi-autonomous organelles that execute numerous life-sustaining tasks in eukaryotic cells. Functioning of mitochondria depends on the adequate action of versatile proteinaceous machineries. Fine-tuning of mitochondrial activity in response to cellular needs involves continuous remodeling of organellar proteome. This process not only includes modulation of various biogenetic pathways, but also the removal of superfluous proteins by adenosine triphosphate (ATP)-driven proteolytic machineries. Accordingly, all mitochondrial sub-compartments are under persistent surveillance of ATP-dependent proteases. Particularly important are highly conserved two inner mitochondrial membrane-bound metalloproteases known as m-AAA and i-AAA (ATPases associated with diverse cellular activities), whose mis-functioning may lead to impaired organellar function and consequently to development of severe diseases. Herein, we discuss the current knowledge of yeast, mammalian, and plant AAA proteases and their implications in mitochondrial function and homeostasis maintenance

Identification of Physiological Substrates and Binding Partners of the Plant Mitochondrial Protease FTSH4 by the Trapping Approach

Maintenance of functional mitochondria is vital for optimal cell performance and survival. This is accomplished by distinct mechanisms, of which preservation of mitochondrial protein homeostasis fulfills a pivotal role. In plants, inner membrane-embedded i-AAA protease, FTSH4, contributes to the mitochondrial proteome surveillance. Owing to the limited knowledge of FTSH4’s in vivo substrates, very little is known about the pathways and mechanisms directly controlled by this protease. Here, we applied substrate trapping coupled with mass spectrometry-based peptide identification in order to extend the list of FTSH4’s physiological substrates and interaction partners. Our analyses revealed, among several putative targets of FTSH4, novel (mitochondrial pyruvate carrier 4 (MPC4) and Pam18-2) and known (Tim17-2) substrates of this protease. Furthermore, we demonstrate that FTSH4 degrades oxidatively damaged proteins in mitochondria. Our report provides new insights into the function of FTSH4 in the maintenance of plant mitochondrial proteome

The anthropogenic pollutants in urban ponds based on the example of Słupsk

In areas of urban infrastructure, ponds play an important role. They are places of rest and recreation, and they facilitate contact between city dwellers and the aquatic environment. They are also a place for living waterflow and ichthyofauna. Urban ponds are susceptible to anthropogenic influences, and their self-cleaning capacity is limited due to their small size. The city of Słupsk is located in northern Poland. Coal combustion in domestic boilers and transport cause dust emissions to be released into the atmosphere. The concentration of particulate matter and heavy metals in PM10 in Słupsk is much higher than in neighbouring village Gać. This affects metals deposition from the atmosphere. Two urban ponds in Słupsk were the object of the research. Sampling station No. 1 was located in the southern part of the Raj Pond situated deep into the forest area, a considerable distance from urban buildings. Sampling station No. 2 was located at the Juniorów Pond located near the city centre. Water samples were taken from a depth of 10 cm. To investigate the deposition from the atmosphere, atmospheric precipitation was collected in a collector located in the city of Słupsk. The concentrations of Li, Al, Cr, Mn, Fe, Ni, Se, As, V, Sr, Cd and Pb were analyzed in the obtained water samples. Measurements were made using an ICP-MS mass spectrometer. From the obtained results, it was observed that the concentrations of Li, Al, Cr, Mn, Fe, Se, Sr and Cd were higher at station No. 2 located near the city centre

The anthropogenic pollutants in urban ponds based on the example of Słupsk

In areas of urban infrastructure, ponds play an important role. They are places of rest and recreation, and they facilitate contact between city dwellers and the aquatic environment. They are also a place for living waterflow and ichthyofauna. Urban ponds are susceptible to anthropogenic influences, and their self-cleaning capacity is limited due to their small size. The city of Słupsk is located in northern Poland. Coal combustion in domestic boilers and transport cause dust emissions to be released into the atmosphere. The concentration of particulate matter and heavy metals in PM10 in Słupsk is much higher than in neighbouring village Gać. This affects metals deposition from the atmosphere. Two urban ponds in Słupsk were the object of the research. Sampling station No. 1 was located in the southern part of the Raj Pond situated deep into the forest area, a considerable distance from urban buildings. Sampling station No. 2 was located at the Juniorów Pond located near the city centre. Water samples were taken from a depth of 10 cm. To investigate the deposition from the atmosphere, atmospheric precipitation was collected in a collector located in the city of Słupsk. The concentrations of Li, Al, Cr, Mn, Fe, Ni, Se, As, V, Sr, Cd and Pb were analyzed in the obtained water samples. Measurements were made using an ICP-MS mass spectrometer. From the obtained results, it was observed that the concentrations of Li, Al, Cr, Mn, Fe, Se, Sr and Cd were higher at station No. 2 located near the city centre