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Author

Tomasz Rudka

Bio: Tomasz Rudka is an academic researcher from Katholieke Universiteit Leuven. The author has contributed to research in topics: PARL & mitochondrial fusion. The author has an hindex of 4, co-authored 6 publications receiving 2521 citations. Previous affiliations of Tomasz Rudka include Nencki Institute of Experimental Biology.

Papers
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Journal ArticleDOI
14 Jul 2006-Cell
TL;DR: Evidence is provided that Optic Atrophy 1 (OPA1), a profusion dynamin-related protein of the inner mitochondrial membrane mutated in dominant optic atrophy, protects from apoptosis by preventing cytochrome c release independently from mitochondrial fusion.

1,444 citations

Journal ArticleDOI
14 Jul 2006-Cell
TL;DR: Findings implicate regulated intramembrane proteolysis in controlling apoptosis in Parl-/- mice, substantiating the importance of PARL in OPA1 processing.

647 citations

Journal Article
TL;DR: Parl-associated rhomboid-like (PARL-like) as mentioned in this paper is an inner mitochondrial membrane rhomboids of unknown function, whose yeast ortholog is involved in mitochondrial fusion.

616 citations

Patent
11 Aug 2006
TL;DR: In this article, the authors decrit a souris transgenique, which ne produit pas la protease mitochondriale PARL de forme rhomboide, and s'avere that le phenotype of cette souris est caracterise par une apoptose massive des lymphocytes B and T.
Abstract: La presente invention concerne le domaine du cancer, plus particulierement le domaine des lymphomes et encore plus particulierement le domaine des tumeurs a lymphocytes B et T. L'invention decrit une souris transgenique qui ne produit pas la protease mitochondriale PARL de forme rhomboide. Il s’avere que le phenotype de cette souris est caracterise par une apoptose massive des lymphocytes B et T. L'invention a donc pour objet des molecules qui peuvent se lier a la PARL et sont capables d'induire l'apoptose des lymphocytes B et T. L'invention concerne egalement l'utilisation de ces molecules pour traiter des cancers a lymphocytes B et T plus communement denomes lymphomes.

1 citations


Cited by
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Journal ArticleDOI
TL;DR: New insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, but a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.
Abstract: BCL-2 family proteins, which have either pro- or anti-apoptotic activities, have been studied intensively for the past decade owing to their importance in the regulation of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. They control the point of no return for clonogenic cell survival and thereby affect tumorigenesis and host-pathogen interactions and regulate animal development. Recent structural, phylogenetic and biological analyses, however, suggest the need for some reconsideration of the accepted organizational principles of the family and how the family members interact with one another during programmed cell death. Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.

4,246 citations

Journal ArticleDOI
TL;DR: Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria, meaning that mitochondria coordinate the late stage of cellular demise.
Abstract: Irrespective of the morphological features of end-stage cell death (that may be apoptotic, necrotic, autophagic, or mitotic), mitochondrial membrane permeabilization (MMP) is frequently the decisive event that delimits the frontier between survival and death. Thus mitochondrial membranes constitute the battleground on which opposing signals combat to seal the cell's fate. Local players that determine the propensity to MMP include the pro- and antiapoptotic members of the Bcl-2 family, proteins from the mitochondrialpermeability transition pore complex, as well as a plethora of interacting partners including mitochondrial lipids. Intermediate metabolites, redox processes, sphingolipids, ion gradients, transcription factors, as well as kinases and phosphatases link lethal and vital signals emanating from distinct subcellular compartments to mitochondria. Thus mitochondria integrate a variety of proapoptotic signals. Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria. These catabolic enzymes as well as the cessation of the bioenergetic and redox functions of mitochondria finally lead to cell death, meaning that mitochondria coordinate the late stage of cellular demise. Pathological cell death induced by ischemia/reperfusion, intoxication with xenobiotics, neurodegenerative diseases, or viral infection also relies on MMP as a critical event. The inhibition of MMP constitutes an important strategy for the pharmaceutical prevention of unwarranted cell death. Conversely, induction of MMP in tumor cells constitutes the goal of anticancer chemotherapy.

3,340 citations

Journal ArticleDOI
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Ilio Vitale3, Stuart A. Aaronson4  +183 moreInstitutions (111)
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Abstract: Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

3,301 citations

Journal ArticleDOI
TL;DR: The authors suggest that PINK1 and Parkin form a pathway that senses damaged mitochondria and selectively targets them for degradation.
Abstract: Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown. Here, we show that expression of PINK1 on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels of PINK1 on healthy, polarized mitochondria, while facilitating the rapid accumulation of PINK1 on mitochondria that sustain damage. PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 and Parkin disrupt Parkin recruitment and Parkin-induced mitophagy at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila melanogaster. In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination.

2,404 citations

Journal ArticleDOI
16 Mar 2012-Cell
TL;DR: This work provides a current view of how mitochondrial functions impinge on health and disease and identifies mitochondrial dysfunction as a key factor in a myriad of diseases, including neurodegenerative and metabolic disorders.

2,266 citations