Growth and Differentiation Factor 15 as a biomarker for mitochondrial myopathy
Publication date: Available online 26 October 2019Source: MitochondrionAuthor(s): Nanna Scharff Poulsen, Karen Lindhardt Madsen, Tessa Munkeboe Hornsyld, Anne-Sofie Vibæk Eisum, Freja Fornander, Astrid Emilie Buch, Mads Godtfeldt Stemmerik, Cristina Ruiz-Ruiz, Thomas Oliver Krag, John VissingAbstractObjectiveWe investigated if Growth and Differentiation Factor 15 (GDF-15) can be used as a biomarker to distinguish patients with mitochondrial myopathy from patients with other myopathies.MethodsSerum GDF-15 was measured in 28 patients with mitochondrial disease, 24 with metabolic myopathies, 27 with muscular dystrophy and 21...
Source: Mitochondrion - October 26, 2019 Category: Biochemistry Source Type: research
The basic machineries for mitochondrial protein quality control
Publication date: Available online 26 October 2019Source: MitochondrionAuthor(s): Carmela Vazquez-Calvo, Tamara Suhm, Sabrina Büttner, Martin OttAbstractMitochondria play pivotal roles in cellular energy metabolism, the synthesis of essential biomolecules and the regulation of cell death and aging. The proper folding, unfolding and degradation of the many proteins active within mitochondria is surveyed by the mitochondrial quality control machineries. Here, we describe the principal components of the mitochondrial quality control system and recent developments in the elucidation of the molecular mechanisms maintaining a f...
Source: Mitochondrion - October 26, 2019 Category: Biochemistry Source Type: research
Extracellular matrix/mitochondria pathway: a novel potential target for sarcopenia
Publication date: Available online 24 October 2019Source: MitochondrionAuthor(s): Aicha Melouane, Mayumi Yoshioka, Jonny St-AmandAbstractSarcopenia is a geriatric syndrome characterized by a progressive and generalized loss of muscle mass, strength, and endurance. Although the mitochondrial hypothesis of sarcopenia has been proposed, it remains a highly debated topic. The age-related declines in skeletal muscle regenerative capacity have been attributed to the changes in the extracellular matrix (ECM) composition. Therefore, mitochondrial deterioration in the muscle may be implicated in the sarcopenic process, and a possib...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
Endoplasmic reticulum stress induced apoptosis and caspase activation is mediated through mitochondria during megakaryocyte differentiation
Publication date: Available online 25 October 2019Source: MitochondrionAuthor(s): Narasaiah Kovuru, Sanjeev Raghuwanshi, Durga Shankar Sharma, Swati Dahariya, Adithya Pallepati, Ravi Kumar GuttiAbstractMegakaryocytopoiesis involves the process of the development of hematopoietic stem cells into megakaryocytes (MKs), which are the specialized cells responsible for the production of blood platelets. Platelets are one of the crucial factors for hemostasis and thrombosis. In terminally differentiated MKs many molecular process such as caspase activation and a massive cytoskeletal rearrangement drive the formation of cytoplasmi...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
Ironing the mitochondria: Relevance to its dynamics
Publication date: Available online 25 October 2019Source: MitochondrionAuthor(s): Mamta Upadhyay, Saloni AgarwalAbstractThe mitochondrion is “jack of many trades and master of one”. Despite being a master in energy generation, it plays a significant role in other cellular processes, including calcium homeostasis, cell death, and iron metabolism. Since mitochondria employ the majority of cellular iron, it plays a central role in the iron homeostasis. Iron could be a major regulator of mitochondrial dynamics as the excess of iron leads to oxidative stress, which causes a disturbance in mitochondrial dynamics. Remarkably,...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
Mitochondrial chaperone, TRAP1 as a potential pharmacological target to combat cancer metabolism
Publication date: Available online 25 October 2019Source: MitochondrionAuthor(s): Balaji Ramkumar, Shrikant P. Dharaskar, Mounika Guntipally, Khanderao Paithankar, Amere Subbarao SreedharAbstractThe stress response forms the most ancient defense system in living cells. Heat shock proteins (Hsps) are highly conserved across species and play major roles in mounting the stress response. The emerging information now suggests that Hsp90 family of chaperones display additional cellular roles contributing to diseases like cancer. For this reason, pharmacological targeting of Hsp90 has emerged as a novel antitumor strategy. Howeve...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
Sensitivity of mitochondrial DNA heteroplasmy detection using Next Generation Sequencing
Publication date: Available online 25 October 2019Source: MitochondrionAuthor(s): María del Mar González, Amanda Ramos, Maria Pilar Aluja, Cristina SantosAbstractAlthough the use of Next Generation Sequencing (NGS) in mitochondrial DNA (mtDNA) studies related to forensic and human genetics has contributed to the report of heteroplasmy at very low levels (lower than 1% and even 0.5%), their detection is not a straightforward process. Our purpose is to establish mitochondrial heteroplasmy detection limits, generating mixed bases at low frequencies by the PCR co-amplification of mtDNA and a nuclear insertion of mitochondria...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
Modular Biogenesis of Mitochondrial Respiratory Complexes
Publication date: Available online 25 October 2019Source: MitochondrionAuthor(s): Mario H. Barros, Gavin P. McStayAbstractMitochondrial function relies on the function of oxidative phosphorylation to synthesise ATP and generate an electrochemical gradient across the inner mitochondrial membrane. These coupled processes are mediated by five multi-subunit complexes that reside in this inner membrane. These complexes are the product of both nuclear and mitochondrial gene products. Defects in the function or assembly of these complexes can lead to mitochondrial diseases due to deficits in energy production and mitochondrial fu...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
The Changing Landscape of Clinical Trials for Mitochondrial Diseases: 2011 to Present
Publication date: Available online 25 October 2019Source: MitochondrionAuthor(s): Delia Khayat, Tracie L. Kurtz, Peter W. StacpooleAbstractWe reviewed the status of interventional clinical trials for primary mitochondrial diseases. Using national and international search engines, we found 48 randomized controlled trials (RCTs) registered as of May 15, 2019. Consilience between lay and professional mitochondrial disease communities to engage in RCTs has increased, as has progress in developing new disease and treatment biomarkers and potential therapies. The continued advancement of general knowledge of mitochondrial biolog...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
In silico simulation of reversible and irreversible swelling of mitochondria: the role of membrane rigidity
Publication date: Available online 25 October 2019Source: MitochondrionAuthor(s): Vladimir I. Makarov, Igor Khmelinskii, Zaza Khuchua, Sabzali JavadovAbstractMitochondria have been widely accepted as the main source of ATP in the cell. The inner mitochondrial membrane (IMM) is important for the maintenance of ATP production and other functions of mitochondria. The electron transport chain (ETC) generates an electrochemical gradient of protons known as the proton-motive force across the IMM and thus produces the mitochondrial membrane potential that is critical to ATP synthesis. One of the main factors regulating the struct...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
Disturbance of mitochondrial functions associated with permeability transition pore opening induced by cis-5-tetradecenoic and myristic acids in liver of adolescent rats
Publication date: Available online 23 October 2019Source: MitochondrionAuthor(s): Cristiane Cecatto, Alexandre Umpierrez Amaral, Alessandro Wajner, Simone Magagnin Wajner, Roger Frigério Castilho, Moacir WajnerAbstractPatients affected by very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency commonly present liver dysfunction whose pathogenesis is poorly known. We demonstrate here that major metabolites accumulating in this disorder, namely cis-5-tetradecenoic acid (Cis-5) and myristic acid (Myr), markedly impair mitochondrial respiration, decreasing ATP production in liver mitochondrial preparations from adolescent r...
Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research
Cetylpyridinium chloride is a potent AMP-activated kinase (AMPK) inducer and has therapeutic potential in cancer
Publication date: Available online 22 October 2019Source: MitochondrionAuthor(s): Sonia A. Allen, Sandipan Datta, Jose Sandoval, Alexey Tomilov, Thomas Sears, Kevin Woolard, James M. Angelastro, Gino A. CortopassiAbstractAMP-activated protein kinase (AMPK) is a eukaryotic energy sensor and protector from mitochondrial/energetic stress that is also a therapeutic target for cancer and metabolic disease. Metformin is an AMPK inducer that has been used in cancer therapeutic trials. Through screening we isolated cetylpyridinium chloride (CPC), a drug known to dose-dependently inhibit mitochondrial complex 1, as a potent and dos...
Source: Mitochondrion - October 23, 2019 Category: Biochemistry Source Type: research
Emerging concepts of mitochondrial dysfunction in Parkinson’s disease progression: Pathogenic and therapeutic implications
Publication date: Available online 22 October 2019Source: MitochondrionAuthor(s): Linchi Rani, Amal Chandra MondalAbstractMitochondria are very dynamic organelle which play a multifactorial role for a broad range of physiological processes inside the cell to maintain neural circuit integrity. They are required for the generation of cellular energy, regulation of calcium homeostasis and controlling programmed cell death. Defective mitochondrial homeostasis is frequently reported in a broad range of neurological disorders. Many lines of evidence suggest that it plays an essential role in aging, and neurodegeneration. Parkins...
Source: Mitochondrion - October 23, 2019 Category: Biochemistry Source Type: research
A novel mutation in the mitochondrial MTND5 gene in a family with MELAS. The relevance of genetic analysis on targeted tissues
We report the case of two members of the same family with a novel mitochondrial DNA (mtDNA) gene variant in the MTND5 gene associated with MELAS syndrome and discuss limitations of genetics studies. The m.13045A>G mutation was detected at very low load in the daughter’s urine cells (5%) and at different levels in the skeletal muscle of both mother (50%) and daughter (84%), being absent in blood, hair and saliva.Our findings suggest that non-invasive genetic assessment in urine cells may not be a sensitive diagnostic method neither a good predictor of disease development in relatives of some families with mtDNA-associated...
Source: Mitochondrion - October 20, 2019 Category: Biochemistry Source Type: research
Fis1 deficiencies differentially affect mitochondrial quality in skeletal muscle
Publication date: Available online 14 September 2019Source: MitochondrionAuthor(s): Zhe Zhang, Danielle A. Sliter, Christopher K.E. Bleck, Shuzhe DingAbstractMitochondrial dynamics and mitophagy are important aspects of mitochondrial quality control, and are linked to neurodegenerative diseases and muscular diseases. Fis1, a protein on the mitochondrial outer membrane, is thought to mediate mitochondrial fission. However, Fis1 null worms and mammalian cells only display mild fission defects but show aberrant mitophagy. To assess Fis1 function in vivo, we generated conditional knock-out Fis1 mice to allow for specific Fis1 ...
Source: Mitochondrion - September 15, 2019 Category: Biochemistry Source Type: research
