Mitochondrial Dynamics: Functional Link with Apoptosis

Mitochondria participate in a variety of physiologic processes, such as ATP production, lipid metabolism, iron-sulfur cluster biogenesis, and calcium buffering. The morphology of mitochondria changes dynamically due to their frequent fusion and division in response to cellular conditions, and these dynamics are an important constituent of apoptosis. The discovery of large GTPase family proteins that regulate mitochondrial dynamics, together with novel insights into the role of mitochondrial fusion and fission in apoptosis, has provided important clues to understanding the molecular mechanisms of cellular apoptosis. In this paper, we briefly summarize current knowledge of the role of mitochondrial dynamics in apoptosis and cell pathophysiology in mammalian cells

A novel insertion pathway of mitochondrial outer membrane proteins with multiple transmembrane segments

The central channel Tom40 of the preprotein translocase of outer membrane (TOM) complex is thought to be responsible for the import of virtually all preproteins synthesized outside the mitochondria. In this study, we analyze the topogenesis of the peripheral benzodiazepine receptor (PBR), which integrates into the mitochondrial outer membrane (MOM) through five hydrophobic transmembrane segments (TMSs) and functions in cholesterol import into the inner membrane. Analyses of in vitro and in vivo import into TOM component–depleted mitochondria reveal that PBR import (1) depends on the import receptor Tom70 but requires neither the Tom20 and Tom22 import receptors nor the import channel Tom40, (2) shares the post-Tom70 pathway with the C-tail–anchored proteins, and (3) requires factors of the mitochondrial intermembrane space. Furthermore, membrane integration of mitofusins and mitochondrial ubiquitin ligase, the MOM proteins with two and four TMSs, respectively, proceeds through the same initial pathway. These findings reveal a previously unidentified pathway of the membrane integration of MOM proteins with multiple TMSs

Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells

Localization of the dynamin-related GTPase Drp1 to mitochondria relies on the mitochondrial fission factor Mff

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

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

New insights into the function and regulation of mitochondrial fission

AbstractMitochondrial morphology changes dynamically by coordinated fusion and fission and cytoskeleton-based transport. Cycles of outer and inner membrane fusion and fission are required for the exchange of damaged mitochondrial genome DNA, proteins, and lipids with those of healthy mitochondria to maintain robust mitochondrial structure and function. These dynamics are crucial for cellular life and death, because they are essential for cellular development and homeostasis, as well as apoptosis. Disruption of these functions leads to cellular dysfunction, resulting in neurologic disorders and metabolic diseases. The cytoplasmic dynamin-related GTPase Drp1 plays a key role in mitochondrial fission, while Mfn1, Mfn2 and Opa1 are involved in fusion reaction. Here, we review current knowledge regarding the regulation and physiologic relevance of Drp1-dependent mitochondrial fission: the initial recruitment and assembly of Drp1 on the mitochondrial fission foci, regulation of Drp1 activity by post-translational modifications, and the role of mitochondrial fission in cell pathophysiology

Peroxisomal Targeting Signal Receptor Pex5p Interacts with Cargoes and Import Machinery Components in a Spatiotemporally Differentiated Manner: Conserved Pex5p WXXXF/Y Motifs Are Critical for Matrix Protein Import

Two isoforms of the peroxisomal targeting signal type 1 (PTS1) receptor, termed Pex5pS and (37-amino-acid-longer) Pex5pL, are expressed in mammals. Pex5pL transports PTS1 proteins and Pex7p-PTS2 cargo complexes to the initial Pex5p-docking site, Pex14p, on peroxisome membranes, while Pex5pS translocates only PTS1 cargoes. Here we report functional Pex5p domains responsible for interaction with peroxins Pex7p, Pex13p, and Pex14p. An N-terminal half, such as Pex5pL(1-243), comprising amino acid residues 1 to 243, bound to Pex7p, Pex13p, and Pex14p and was sufficient for restoring the impaired PTS2 import of pex5 cell mutants, while the C-terminal tetratricopeptide repeat motifs were required for PTS1 binding. N-terminal Pex5p possessed multiple Pex14p-binding sites. Alanine-scanning analysis of the highly conserved seven (six in Pex5pS) pentapeptide WXXXF/Y motifs residing at the N-terminal region indicated that these motifs were essential for the interaction of Pex5p with Pex14p and Pex13p. Moreover, mutation of several WXXXF/Y motifs did not affect the PTS import-restoring activity of Pex5p, implying that the binding of Pex14p to all of the WXXXF/Y sites was not a prerequisite for the translocation of Pex5p-cargo complexes. Pex5p bound to Pex13p at the N-terminal part, not to the C-terminal SH3 region, via WXXXF/Y motifs 2 to 4. PTS1 and PTS2 import required the interaction of Pex5p with Pex14p but not with Pex13p, while Pex5p binding to Pex13p was essential for import of catalase with PTS1-like signal KANL. Pex5p recruited PTS1 proteins to Pex14p but not to Pex13p. Pex14p and Pex13p formed a complex with PTS1-loaded Pex5p but dissociated in the presence of cargo-unloaded Pex5p, implying that PTS cargoes are released from Pex5p at a step downstream of Pex14p and upstream of Pex13p. Thus, Pex14p and Pex13p very likely form mutually and temporally distinct subcomplexes involved in peroxisomal matrix protein import

Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy

El presente trabajo de investigación nace de la motivación que generó en los investigadores el documento del doctor Jorge Túa Pereda titulado “La Docencia de la Contabilidad”, en donde señalaba su preocupación por la falta de enseñanza de la teoría contable en las universidades que formaban a Contadores Públicos. Esta falencia podría llevar a un retroceso y hasta a la desaparición de la ciencia Contable. Ante tal situación, los investigadores pretendieron conocer la realidad de la enseñanza y para ello tomaron cuatro programas estudios de los primeros cursos de sendas universidades y sendas carreras de Contador Públicos de cuatro países, Argentina, Chile, Colombia y México, que fueron elegidos en forma aleatoria. Lo primero que se procedió fue a realizar una revisión de literatura que permitió establecer una definición de teoría contable y una caracterización de ella, distinguiendo algunas teorías o escuelas (no todas necesariamente, siendo posible que existan otras no consideradas) que podrían ilustrar el cuerpo de conocimiento que involucraba. Posteriormente se procedió a realizar una investigación exploratoria del tipo cualitativa, analizando las unidades temáticas de cada programa que se consiguió de esas carreras, poniendo atención en cómo se abordaban los temas y esperando que hubiera alguna mención a las escuelas o teorías que fueron formalizadas. El resultado de esta investigación evidenció que no hay una referencia expresa a las teorías que señala este estudio inicial que los investigadores efectuaron, y que existe una exacerbación de la enseñanza de la normativa contable por sobre la teoría, especialmente en las universidades chilenas y mexicanas, en donde hay mayor énfasis en el registro que en el desarrollo de teorías.This research stems from the motivation generated by researcher’s document Dr. Jorge Túa Pereda entitled "The Teaching of Accounting" where stated its concern about the lack of accounting theory teaching in universities which were to CPAs. This short coming could lead to a decline and even the disappearance of Accounting Science. In this situation, the researchers sought to understand the reality of teaching and it took studies of the first courses of separate universities and paths racing Public Accountant four countries, Argentina, Chile, Colombia and Mexico four programs that were chosen in the form random. The first thing we proceeded was to conduct a literature review could establish a definition of accounting theory and characterization of it, distinguishing some theories or schools (no tall necessarily be possible that there are other not considered) that could illustrate the body knowledge involved. He then proceeded to conduct an exploratory investigation of qualitative nature, analyzing the thematic units of each program was achieved in those races, paying attention to how the issues were ad dressed and hoping there was some mention of school so theories that were formalized. The result of this research showed that there is no express reference to theories pointing this initial study there searchers made, and that there is an exacerbation of teaching accounting standards by the theory, especially in the Chilean and Mexican universities, where there is greater emphasis on record that in the development of theories.Facultad de Ciencias Económica