Showing papers by "Thomas Langer published in 2008"
TL;DR: Current knowledge on surveillance strategies that limit mitochondrial damage and ensure cellular integrity and their role in human disease are summarized.
Abstract: Dysfunction of mitochondria has severe cellular consequences and is linked to ageing and neurodegeneration in human. Several surveillance strategies have evolved that limit mitochondrial damage and ensure cellular integrity. Intraorganellar proteases conduct protein quality control and exert regulatory functions, membrane fusion and fission allow mitochondrial content mixing within a cell, and the autophagic degradation of severely damaged mitochondria protects against apoptosis. Here, we will summarize the current knowledge on these surveillance strategies and their role in human disease.
498 citations
TL;DR: Conditional gene targeting of murine Phb2 is used to define cellular activities of prohibitins and assign an essential function for the formation of mitochondrial cristae to prohibitingins and suggest a coupling of cell proliferation to mitochondrial morphogenesis.
Abstract: Prohibitins comprise an evolutionarily conserved and ubiquitously expressed family of membrane proteins with poorly described functions. Large assemblies of PHB1 and PHB2 subunits are localized in the inner membrane of mitochondria, but various roles in other cellular compartments have also been proposed for both proteins. Here, we used conditional gene targeting of murine Phb2 to define cellular activities of prohibitins. Our experiments restrict the function of prohibitins to mitochondria and identify the processing of the dynamin-like GTPase OPA1, an essential component of the mitochondrial fusion machinery, as the central cellular process controlled by prohibitins. Deletion of Phb2 leads to the selective loss of long isoforms of OPA1. This results in an aberrant cristae morphogenesis and an impaired cellular proliferation and resistance toward apoptosis. Expression of a long OPA1 isoform in PHB2-deficient cells suppresses these defects, identifying impaired OPA1 processing as the primary cellular defect in the absence of prohibitins. Our results therefore assign an essential function for the formation of mitochondrial cristae to prohibitins and suggest a coupling of cell proliferation to mitochondrial morphogenesis.
481 citations
TL;DR: A new function of MFN2-tethering the endoplasmic reticulum and mitochondria to control the efficiency of mitochondrial uptake of Ca2+ ions is demonstrated.
111 citations
Patent•
02 Jul 2008
TL;DR: In this article, a means and methods for therapeutic intervention of mitochondrial disorders or diseases, in particular to a method for the treatment, prevention and/or amelioration of a disorder or disease correlated with mitochondrial dysfunction, a mitochondrial disorder or diseases or disorders characterized by an altered OPA1 processing, are discussed.
Abstract: The present invention relates to means and methods for therapeutic intervention of mitochondrial disorders or diseases, in particular to a method for the treatment, prevention and/or amelioration of a disorder or disease correlated with mitochondrial dysfunction, a mitochondrial disorder or disease or a disorder or disease characterized by an altered OPA1 processing. Thereby, a pharmaceutically active amount of a compound capable of modulating the activity of an oligomeric complex comprising Afg3Ι1 and/or Afg3Ι2 or (a) variant(s) thereof is administered to a patient in need of medical intervention. The present invention also relates to the use of an oligomeric complex comprising Afg3Ι1 and/or Afg3Ι2 or (a) variant(s) thereof for the preparation of a pharmaceutical composition for the mentioned therapeutic intervention. The present invention further relates to a method of screening for a compound capable of modulating the activity of an oligomeric complex comprising Afg3Ι1 and/or Afg3Ι2 or (a) variant(s) thereof comprising the use of OPA1.
4 citations