Mitochondrial ATP synthase: architecture, function and pathology

Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F1, situated in the mitochondrial matrix, and Fo, located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the human complex V assembly process. The elucidation of more nuclear genetic defects will guide physio(patho)logical studies, paving the way for future therapeutic interventions

Choroid plexus failure in the Kearns-Sayre syndrome

<p>Abstract</p> <p>The Kearns-Sayre syndrome is a mitochondrial disorder (generally due to mitochondrial DNA deletions) that causes ophthalmoplegia, retinopathy, ataxia and brain abnormalities such as leukoencephalopathy. In this syndrome, the choroid plexus epithelial cells, unlike brain cells, are greatly enlarged and granular, consistent with their inability to adequately transport folate from blood into cerebrospinal fluid (CSF), and homovanillic acid (a dopamine metabolite) from CSF into blood. This inability to transport folates from blood into CSF (and brain) adequately, causes cerebral folate deficiency that can be partially reversed by very high doses of reduced folates. The Kearns-Sayre syndrome is a disease that interferes with key choroid plexus functions and is a cause of generalized choroid plexus failure.</p

Hunting Superfluous Locks with Model Checking

International audienceParallelization of existing sequential programs to increase their performance and exploit recent multi and many-core architectures is a challenging but inevitable effort. One increasingly popular paral-lelization approach is based on OpenMP, which enables the designer to annotate a sequential program with constructs specifying the parallel execution of code blocks. These constructs are then interpreted by the OpenMP compiler and runtime, which assigns blocks to threads running on a parallel architecture. Although this scheme is very flexible and not (very) intrusive, it does not prevent the occurrence of synchronization errors (e.g., deadlocks) or data races on shared variables. In this paper, we propose an iterative method to assist the OpenMP parallelization by using formal methods and verification. In each iteration, potential data races are identified by applying to the OpenMP program a lockset analysis , which computes the set of shared variables that potentially need to be protected by locks. To avoid the insertion of superfluous locks, an abstract , action-based formal model of the OpenMP program is extracted and analyzed using the ACTL on-the-fly model checker of the CADP formal verification toolbox. We describe the method, compare it with existing work, and illustrate its practical use