Tuesday 29 August 2017

Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions

Wong HS, Dighe PA, Mezera V, Monternier PA, Brand MD

http://www.jbc.org/content/early/2017/08/24/jbc.R117.789271

  • Relative contributions of mitochondrial superoxide/ hydrogen peroxide production by different sites in the electron transport chain, under different conditions

Monday 14 August 2017

Endocrine disruptors induce perturbations in endoplasmic reticulum and mitochondria of human pluripotent stem cell derivatives

Rajamani U, Gross AR, Ocampo C, Andres AM, Gottlieb RA, Sareen D

https://www.nature.com/articles/s41467-017-00254-8

  • Study of the effect of common man-made chemicals (specifically endocrine distrupting chemicals, or EDCs)  on human-induced pluipotent stem cells
  • The authors suggest that exposure to perfluoro-octanoic acid (found in cookware), tributyltin (found in house dust), and butylhydroxytoluene (found in food additives) can induce endoplasmic reticulum stress, perturb inflammatory and cell-death signalling pathways (NF-kB and p53), diminish mitochondrial respiratory gene expression, spare respiratory capacity and ATP levels in stem cells.
  • Consequently, normal secretion of appetite control hormones is affected.
  • The authors provide this as mechanistic evidence that repeated exposure to these "obesogenic" endocrine distrupting chemicals in utero can alter some genetically pre-disposed individuals' normal metabolic control, setting them up for long-term obesity.

In vivo imaging reveals mitophagy independence in the maintenance of axonal mitochondria during normal aging

Cao X, Wang H, Wang Z, Wang Q, Zhang S, Deng Y, Fang Y

http://onlinelibrary.wiley.com/doi/10.1111/acel.12654/epdf

  • Study of mitophagy and aging in Drosophila
  • Mitochondria become fragmented in aged mitochondria
  • Lack of Pink1 or Parkin does not lead to the accumulation of axonal mitochondria or axonal degeneration
  • Knockdown of core mitphagy genes Atg12 or Atg17 has little effect on turnover of axonal mitochondria or axonal integrity suggesting that mitophagy is not necessary for axonal maintainence, regardless of whether it is Pink1-Parkin dependent
  • Adult onset of neuronal downregulation of fission-fusion but not mitophagy genes dramatically accelerated features of aging
  • Thought: Is this partly because Drosophila generally has a short lifespan and, in some sense, die before they have the chance to get old? Are these results observable in other, longer-lived, species?

Tuesday 8 August 2017

Interesting papers

The Mitochondrial Basis of Aging
Nuo Sun, Richard J. Youle and Toren Finkel
Molecular Cell 
http://www.sciencedirect.com/science/article/pii/S1097276516000812
  • An interesting review on the theory that mitochondrial decline contributes to ageing.
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype
Christopher D. Wiley, Michael C. Velarde, Pacome Lecot, ..., Akos A. Gerencser, Eric Verdin, Judith Campisi
Cell Metabolism 
http://www.sciencedirect.com/science/article/pii/S1550413115005781
  •  How mitochondrial dysfunction can induce senescence in proliferative cell types. Such cells have lower NAD+/NADH ratios. Progeroid mtDNA mutator mice accumulate sensescent cells with a mitochondrially-associated senescent secretory phenotype (MiDAS SASP).
Transit and integration of extracellular mitochondria in human heart cells
Douglas B. Cowan, Rouan Yao, Jerusha K. Thedsanamoorthy, David Zurakowski, Pedro J. del Nido, James D. McCully
Biorxiv
  • Transplanting isolated mitochondria from healthy tissue into ischaemic heart tissue can be internalised within minutes, fuse to the mitochondrial network, decrease cell death, increase energy production and improve contractile function

Mitochondrial DNA heteroplasmy is shared between human liver lobes
Manja  Wachsmuth, Alexander  Hübner, Roland  Schröder, ..., Mark Stoneking
Biorxiv
http://www.biorxiv.org/node/46200.full
  • Heteroplasmy distributions in multiple liver lobes from the same individual suggest sharing of heteroplasmy
Segregation of mitochondrial DNA mutations in the human placenta: implication for prenatal diagnosis of mtDNA disorders
Pauline Vachin, Elodie Adda-herzog, Gihad Chalouhi, ..., Julie Steffann
Journal Medical Genetics
  • Distribution of heteroplasmy for multiple samples per individual in the placenta
Mammalian Mitochondria and Aging: An Update
Timo E.S. Kauppila, Johanna H.K. Kauppila, Nils-Göran Larsson 
Cell Metabolism
  • Review on the mitochondrial theory of ageing 
Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins 
Tatiana Tkatch, Elisa Greotti, Gytis Baranauskas, ... and Israel Sekler
http://www.pnas.org/content/114/26/E5167.full
PNAS 
  • Reversible, tunable, optogenetic control of mitochondrial membrane potential using channelrhodopsins
 
Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence
Caterina Tezze, Vanina Romanello, Maria Andrea Desbats, Gian Paolo Fadin, ...,  Luca Scorrano, Marco Sandri
Cell Metabolism
  •   Disturbing the mitochondrial network through OPA1 deletion in muscle may induce faster ageing across distal organs

Mesenchymal stem cells sense mitochondria released from damaged cells as danger signals to activate their rescue properties
 Meriem Mahrouf-Yorgov, Lionel Augeul, Claire Crola Da Silva, Maud Jourdan, ..., Anne-Marie Rodriguez
Cell Death & Differentiation
  •   Mesenchymal cells can 'sense danger' by taking up and degrading mitochondria from stressed cells

The mitochondrial respiratory chain is essential for haematopoietic stem cell function
Elena Ansó,  Samuel E. Weinberg,  Lauren P. Diebold,  Benjamin J. Thompson, ..., Navdeep S. Chandel
Nature Cell Biology
  • OXPHOS is required for differentiation of haematopoietic stem cells 
Heteroplasmic Shifts in Tumor Mitochondrial Genomes Reveal Tissue-specific Signals of Relaxed and Positive Selection
Grandhi S, Bosworth C, Maddox W, Sensiba C, Akhavanfard S, Ni Y, LaFramboise T
https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddx172
Human Molecular Genetics
  •  Signs of positive selection for mitochondrial DNA mutations in certain cancers
 

Interesting papers

MitoNEET-dependent formation of intermitochondrial junctions
Alexandre Vernay, Anna Marchetti, Ayman Sabra, Tania N. Jauslin, Manon Rosselin, Philipp E. Scherer, Nicolas Demaurex, Lelio Orci, and Pierre Cosson 
PNAS
http://www.pnas.org/content/114/31/8277.full
  • MitoNEET, a factor which contributes to the formation of inter-mitochondrial junctions is knocked out. Network becomes more fragmented and there are fewer mitochondria.

Hypothalamic stem cells control ageing speed partly through exosomal miRNAs
Yalin Zhang, Min Soo Kim, Baosen Jia, Jingqi Yan, Juan Pablo Zuniga-Hertz, Cheng Han & Dongsheng Cai
Nature
https://www.nature.com/nature/journal/v548/n7665/full/nature23282.html
  • Secretions from stem cells in the hypothalamus, consisting of exosomes containing miRNAs, can slow down ageing phenotypes. The hypothalamus becomes an inflammatory environment with age. Modifying stem cells to become resistant to inflammation (via the NF-kB pathway) and implanting them into brains of mid-aged mice can slow down ageing.

Increased mitochondrial fusion allows the survival of older animals in diverse C. elegans longevity pathways
Snehal N. Chaudhari & Edward T. Kipreos
Nature Communications
https://www.nature.com/articles/s41467-017-00274-4
  • Mitochondrial fusion is permissive of extended lifespan, but not sufficient.

Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila
Nikolay P. Kandul, Ting Zhang, Bruce A. Hay & Ming Guo
Nature Communications
  • Mitophagy is able to alter heteroplasmy levels of a deleterious mtDNA deletion mutation in Drosophila. Overexpression of PINK1 and Parkin produce large reductions in the frequency of deleterious mutations.