CLPP-Null Eukaryotes with Excess Heme Biosynthesis Show Reduced L-arginine Levels, Probably via CLPX-Mediated OAT Activation.

The serine peptidase CLPP is conserved among bacteria, chloroplasts, and mitochondria. In humans and mice, its loss causes Perrault syndrome, which presents with growth deficits, infertility, deafness, and ataxia. In the filamentous fungus , CLPP loss leads to longevity.

The impact of biomembranes and their dynamics on organismic aging: insights from a fungal aging model.

Biomembranes fulfill several essential functions. They delimitate cells and control the exchange of compounds between cells and the environment. They generate specialized cellular reaction spaces, house functional units such as the respiratory chain (RC), and are involved in content trafficking.

Impact of Mitochondrial Architecture, Function, Redox Homeostasis, and Quality Control on Organismic Aging: Lessons from a Fungal Model System.

Mitochondria are eukaryotic organelles with various essential functions. They are both the source and the targets of reactive oxygen species (ROS). Different branches of a mitochondrial quality control system (mQCS), such as ROS balancing, degradation of damaged proteins, or whole mitochondria, can mitigate the adverse effects of ROS stress.

Sterile Mutant pro34 Is Impaired in Respiratory Complex I Assembly.

The formation of fruiting bodies is a highly regulated process that requires the coordinated formation of different cell types. By analyzing developmental mutants, many developmental factors have already been identified. Yet, a complete understanding of fruiting body formation is still lacking.

CLiB - a novel cardiolipin-binder isolated data-driven and screening.

Cardiolipin, the mitochondria marker lipid, is crucially involved in stabilizing the inner mitochondrial membrane and is vital for the activity of mitochondrial proteins and protein complexes. Directly targeting cardiolipin by a chemical-biology approach and thereby altering the cellular concentration of "available" cardiolipin eventually allows to systematically study the dependence of cellular processes on cardiolipin availability. In the present study, physics-based coarse-grained free energy calculations allowed us to identify the physical and chemical properties indicative of cardiolipin selectivity and to apply these to screen a compound database for putative cardiolipin-binders.

Lifespan Extension of Mic60-Subcomplex Mutants Depends on Cardiolipin Remodeling.

Function of mitochondria largely depends on a characteristic ultrastructure with typical invaginations, namely the cristae of the inner mitochondrial membrane. The mitochondrial signature phospholipid cardiolipin (CL), the FF-ATP-synthase, and the 'mitochondrial contact site and cristae organizing system' (MICOS) complex are involved in this process. Previous studies with demonstrated that manipulation of MICOS leads to altered cristae structure and prolongs lifespan.

To die or not to die - How mitochondrial processes affect lifespan of Podospora anserina.

The filamentous ascomycete Podospora anserina is a well-established model system to study organismic aging. Its senescence syndrome has been investigated for more than fifty years and turned out to have a strong mitochondrial etiology. Several different mitochondrial pathways were demonstrated to affect aging and lifespan.

Lifespan Increase of by Oleic Acid Is Linked to Alterations in Energy Metabolism, Membrane Trafficking and Autophagy.

The maintenance of cellular homeostasis over time is essential to avoid the degeneration of biological systems leading to aging and disease. Several interconnected pathways are active in this kind of quality control. One of them is autophagy, the vacuolar degradation of cellular components.

Aging of Leads to Alterations of OXPHOS and the Induction of Non-Mitochondrial Salvage Pathways.

The accumulation of functionally impaired mitochondria is a key event in aging. Previous works with the fungal aging model demonstrated pronounced age-dependent changes of mitochondrial morphology and ultrastructure, as well as alterations of transcript and protein levels, including individual proteins of the oxidative phosphorylation (OXPHOS). The identified protein changes do not reflect the level of the whole protein complexes as they function in-vivo.

Mitochondrial Phospholipid Homeostasis Is Regulated by the i-AAA Protease PaIAP and Affects Organismic Aging.

Mitochondria are ubiquitous organelles of eukaryotic organisms with a number of essential functions, including synthesis of iron-sulfur clusters, amino acids, lipids, and adenosine triphosphate (ATP). During aging of the fungal aging model , the inner mitochondrial membrane (IMM) undergoes prominent morphological alterations, ultimately resulting in functional impairments. Since phospholipids (PLs) are key components of biological membranes, maintenance of membrane plasticity and integrity via regulation of PL biosynthesis is indispensable.

Impaired FF-ATP-Synthase Dimerization Leads to the Induction of Cyclophilin D-Mediated Autophagy-Dependent Cell Death and Accelerated Aging.

Mitochondrial FF-ATP-synthase dimers play a critical role in shaping and maintenance of mitochondrial ultrastructure. Previous studies have revealed that ablation of the FF-ATP-synthase assembly factor PaATPE of the ascomycete strongly affects cristae formation, increases hydrogen peroxide levels, impairs mitochondrial function and leads to premature cell death. In the present study, we investigated the underlying mechanistic basis.

A Network of Pathways Controlling Cellular Homeostasis Affects the Onset of Senescence in .

Research on unraveled a network of molecular pathways affecting biological aging. In particular, a number of pathways active in the control of mitochondria were identified on different levels. A long-known key process active during aging of is the age-related reorganization of the mitochondrial DNA (mtDNA).

Simultaneous Ablation of the Catalytic AMPK α-Subunit SNF1 and Mitochondrial Matrix Protease CLPP Results in Pronounced Lifespan Extension.

Organismic aging is known to be controlled by genetic and environmental traits. Pathways involved in the control of cellular metabolism play a crucial role. Previously, we identified a role of PaCLPP, a mitochondrial matrix protease, in the control of the mitochondrial energy metabolism, aging, and lifespan of the fungal aging model .

Classification and Nomenclature of Metacaspases and Paracaspases: No More Confusion with Caspases.

Metacaspases and paracaspases are proteases that were first identified as containing a caspase-like structural fold (Uren et al., 2000). Like caspases, meta- and paracaspases are multifunctional proteins regulating diverse biological phenomena, such as aging, immunity, proteostasis and programmed cell death.

Role of sorting nexin PaATG24 in autophagy, aging and development of Podospora anserina.

Sorting nexins are a conserved protein family involved in vesicle transport, membrane trafficking and protein sorting. The sorting nexin ATG24/SNX4 has been demonstrated to be involved in different autophagy pathways and in endosomal trafficking. However, its impact on cellular quality control and on aging and development is still elusive.

Loss of the selective autophagy receptor p62 impairs murine myeloid leukemia progression and mitophagy.

Autophagy maintains hematopoietic stem cell integrity and prevents malignant transformation. In addition to bulk degradation, selective autophagy serves as an intracellular quality control mechanism and requires autophagy receptors, such as p62 (SQSTM1), to specifically bridge the ubiquitinated cargos into autophagosomes. Here, we investigated the function of p62 in acute myeloid leukemia (AML) in vitro and in murine in vivo models of AML.

AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to trigger mitophagic cell death in glioma cells.

Unlabelled: In most cases, macroautophagy/autophagy serves to alleviate cellular stress and acts in a pro-survival manner. However, the effects of autophagy are highly contextual, and autophagic cell death (ACD) is emerging as an alternative paradigm of (stress- and drug-induced) cell demise. AT 101 ([-]-gossypol), a natural compound from cotton seeds, induces ACD in glioma cells as confirmed here by CRISPR/Cas9 knockout of ATG5 that partially, but significantly rescued cell survival following AT 101 treatment.

Quercetin-Induced Lifespan Extension in Requires Methylation of the Flavonoid by the -Methyltransferase PaMTH1.

Quercetin is a flavonoid that is ubiquitously found in vegetables and fruits. Like other flavonoids, it is active in balancing cellular reactive oxygen species (ROS) levels and has a cyto-protective function. Previously, a link between ROS balancing, aging, and the activity of -methyltransferases was reported in different organisms including the aging model Here we describe a role of the -adenosylmethionine-dependent -methyltransferase PaMTH1 in quercetin-induced lifespan extension.

Impact of F1Fo-ATP-synthase dimer assembly factors on mitochondrial function and organismic aging.

In aerobic organisms, mitochondrial FF-ATP-synthase is the major site of ATP production. Beside this fundamental role, the protein complex is involved in shaping and maintenance of cristae. Previous electron microscopic studies identified the dissociation of FF-ATP-synthase dimers and oligomers during organismic aging correlating with a massive remodeling of the mitochondrial inner membrane.

Guidelines and recommendations on yeast cell death nomenclature.

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cel-lular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing.

Role of Prion protein in premature senescence of human fibroblasts.

Prion protein (PrP) is essentially known for its capacity to induce neurodegenerative prion diseases in mammals caused by a conformational change in its normal cellular isoform (PrP) into an infectious and disease-associated misfolded form, called scrapie isoform (PrP). Although its sequence is highly conserved, less information is available on its physiological role under normal conditions. However, increasing evidence supports a role for PrP in the cellular response to oxidative stress.

A novel role of the mitochondrial permeability transition pore in (-)-gossypol-induced mitochondrial dysfunction.

Gossypol, a natural polyphenolic compound from cotton seeds, is known to trigger different forms of cell death in various types of cancer. Gossypol acts as a Bcl-2 inhibitor that induces apoptosis in apoptosis-competent cells. In apoptosis-resistant cancers such as glioblastoma, it triggers a non-apoptotic type of cell death associated with increased oxidative stress, mitochondrial depolarisation and fragmentation.