Appetite regulation is controlled in part by neurons in the lateral hypothalamus, which secrete neuropeptides in response to signals from the body about its energy reserves. In particular, a pair of neuron populations called AGRP (agouti-gene related protein) and POMC (pro-opiomelanocortin) appear to have an opposing effect, with AGRP stimulating feeding and POMC inhibiting it. In this month's issue of Cell, the effect of mitochondrial dynamics on both neuronal populations has been investigated by Dietrich et al and Schneeberger et al. In AGRP neurons, food deprivation leads to a breakup of the mitochondrial network established in the normal-chow diet, whereas feeding of a high fat diet leads to greater aggregation of the mitochondrial network. This effect appears to be population-specific, and has the effect of causing weight gain by increased fat mass.


Knockout of mfn1 does not lead to phenotypic variation on standard chow diet, but leads to fat mass gain in female mice on a high fat diet. No effect is observed in males. Mfn2 knockout leads to decreased weight gain in female mice fed ad libitum on normal chow, with the only observed compensating factor being an increase in respiratory exchange ratio (a measurement of the use of glucose instead of fat in metabolism, which AGRP neurons are believed to play a role in regulating). Both genders gained less weight on a high fat diet if mfn2 was knocked out.

The regulation of mitochondrial DNA copy number in glioblastoma cells

The regulation of mitochondrial DNA copy number in glioblastoma cells


Embryonic stem cells and cancer cells share a number of similarities. Both are highly proliferative (stem cells needing to find a tissue to differentiate at, and cancers are malignant by their nature), glycolytic and have a low copy number of mtDNA. This study compares human neuronal stem cells (hNSCs) and a highly malignant brain cancer called glioblastoma multiforme (GBM). It was shown that hNSCs increase their mtDNA copy number in a cell-specific way during differentiation to a mtDNA "setpoint". When induced to differentiate, GBM fails to match hNSCs expansion in copy number, patterns of gene expression and increased respitatory capacity. However, if mtDNAs are depleted from a GBM and transferred to a mouse, if a tumour manages to form, it is observed that the mtDNA copy number is recovered to in vitro levels, indicating GBM also has an mtDNA setpoint. It is interesting to note that, once mtDNA was depleted from GBM cells and allowed to form a tumour in nude mice, the survival time from largest to smallest was the following: 0.2% (>100 days), 3% (~95 days), 100% (~85 days), 20% (~81 days) and 50% (~78 days), where the percentage indicates the amount of mtDNA remaining in the GBM cells before transfer.

The regulatory role of mitochondria in capacitative calcium entry.

The regulatory role of mitochondria in capacitative calcium entry.

http://www.sciencedirect.com/science/article/pii/S0005272806001137

Mitochondria can uptake calcium by using a uniport in the mitochondrial inner membrane. This uniport is driven by the membrane potential. The uniport has a low affinity for calcium. This implies that mitochondria are not able to take up calcium very efficiently. It is observed, however, that mitochondria do take up calcium and this happens more efficiently than one would expect based on the low affinity of the uniport. This can be explained by the discovery that locally there can be high concentrations of calcium (much higher than the global concentration of calcium in the cytoplasm) which enables the mitochondria to efficiently uptake calcium. Local high concentrations of calcium appear close to calcium channels in the endoplasmic reticulum (ER) and the plasma membrane (PM). 

           The ER is the cell's biggest calcium store and the calcium concentration in the ER can be 3-4 orders of magnitude larger than the concentration in the cytosol. The opening of calcium channels in the ER, which enables calcium to passively flow into the cytosol, depends on the concentration of calcium in the cytosol ([Cacyt]). A higher [Cacyt] induces the opening of the calcium channels in the ER. This positive feedback system is called Calcium-Induced Calcium Release (CICR). If the [Cacyt]  rises above a certain value, however, there is a negative feedback on IP_3-receptor calcium channels (which let calcium flow from the ER into the cytoplasm). This negative feedback inhibits the release of calcium from the ER and consequently decreases the capacitative calcium entry (CCE). This eventually stops the calcium signal in the cell.

       Mitochondria in the vicinity of calcium channels of the ER will take up calcium. This lowers the local [Cacyt] and can prevent the [Cacyt] from reaching the level at which it starts to give negative feedback to calcium channels in the ER. Mitochondria can therefore inhibit negative feedback on IP_3-receptor calcium channels. This stimulates the depletion of calcium stores and also stimulates CCE.
A concentration of calcium in the mitochondrial matrix that is too high can lead to damaged mitochondrial function consequently stops mitochondrial calcium uptake. This will lead to an increase in [Cacyt] and this stimulates negative feedback to the calcium channels. By forming mitochondrial networks, the concentration of calcium inside the mitochondria can be kept at a lower level since the calcium will spread throughout the network. This means that more calcium can be taken up by the mitochondria and less negative feedback will be given to the calcium channels. The formation of mitochondrial networks can therefore lead to a longer effectiveness of the calcium signal.

Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): Formation of mitoptotic bodies and extrusion of mitochondrial material from the cell

Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis):
Formation of mitoptotic bodies and extrusion of mitochondrial material from the cell

When mitochondria are faulty, what is often observed is mitochondrial autophagy or mitophagy, where a subset of the mitochondrial population are digested by autophagosomes. In this paper, another pathway is observed after damage to the whole mitochondrial population. As a model, highly glycolytic HeLa cells are studied. Respiratory chain inhibitors and uncouplers (which induce ROS production and hydrolyse ATP in mitochondria) were applied. This was observed to cause fission of the mitochondrial network, migration of mitochondria to the perinuclear space, accumulation of mitochondria into a vesicle and then its subsequent expulsion by fusing to the plasma membrane.

The Role of Mitochondrial Electron Transport in Tumorigenesis and Metastasis

The Role of Mitochondrial Electron Transport in Tumorigenesis and Metastasis


The role of electron transport in metastasis (formation of secondary tumors) and tumorigenesis (the creation of cancer cells) is poorly understood. This review collects evidence to suggest that there exists a bioenergetic landscape (bell curve) for malignancy in tumors, which must optimise glycolysis versus oxidative phosphorylation (OXPHOS) as a means of energy production. Glycolysis is an anaerobic respiration pathway, which produces less energy than mitochondrial oxidative phosphorylation, but produces many reactive oxygen species and activates malignancy pathways. On the other hand, OXPHOS correlates with more differentiated tumor cells but also anchorage independent cell growth (anoikis resistance) and metastatic potential. This highlights the need for a cancer cell to balance OXPHOS and glycolytic energy production.

Coastal Physical Features in West Africa Shape the Genetic Structure of the Bonga Shad

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793960/

In this paper the genetic diversity of the fish E. Fimbriata that lives along the west coast of Africa is studied. In total 480 fish are sampled and their nuclear DNA is extracted. They then studied the variability in seven loci using an EPIC (exon-primed, intron-crossing polymerase chain reaction) method and used MCMC methods to find the number of parental populations.
         The results they found were somewhat different from earlier studies on these fish in the same regions. In an earlier study, they had looked at variability in mtDNA. This study using mtDNA found three genetically different groups: 1) a northern group extending from Mauritania to Guinea, 2) a central group distributed from Côte d’Ivoire to Cameroon, and 3) a southern group with populations extending from Gabon to Angola. Also, they found a correlation between geographical distance and genetic differentation (the larger the geographical distance, the more genetic differences).
        The study in this paper found genetic differentiation at finer scale, so within the three groups found in the mtDNA study, they found genetically distinct samples whereas these samples appeared genetically the same using the mtDNA markers. Also, this paper found no correlation between the geographical distance and genetic differentation. Sam suggested that this might be because maybe only the male fish move away from where they are born. If the females of a certain population tend not to migrate then the mtDNA of that population will not mix with that of a different population and so you expect to see more difference in mtDNA as the geographical distances become larger. The nuclear DNA of different populations then does mix because of the migrating males.

The Role of Dynamin-Related Protein 1, a Mediator of Mitochondrial Fission, in Apoptosis

The Role of Dynamin-Related Protein 1, a Mediator of Mitochondrial Fission, in Apoptosis


Apoptosis is a form of programmed cell-death, where a cell decides to kill itself in a controlled manner following a stress signal. A number of physiological changes occur inside the cell during apoptosis, one of which is the fragmentation of the mitochondrial network. Drp1 is an important protein involved in mitochondrial fission and can be seen to translocate from the cytosol to the outer membrane of mitochondria before fission. This paper finds that, in the COS-7 immortalized monkey kidney cell line, blocking the function of Drp1 prevents: mitochondrial fragmentation; the loss of mitochondrial membrane potential; the leaking of cytochrome c into the cytoplasm; and crucially, can block apoptosis itself.

Evolution of mitochondrial gene content: gene loss and transfer to the nucleus

Evolution of mitochondrial gene content: gene loss and transfer to the nucleus

adams2003mitochondrial
http://www.ncbi.nlm.nih.gov/pubmed/14615181

Eukaryotic relationships with mitochondria are largely accepted to be the result of an endosymbiotic event between an ancestral eukaryote and a "proto-mitochondrion". Since this event, genes encoding functional aspects of the mitochondrion have been transferred to the eukaryotic nucleus -- for reasons that are unclear but may be related to increased genetic control and/or stability. This review describes current understanding of this process, including the different extents to which it has occurred in different lineages across life. Rickettsia looks perhaps a bit like a precursor mitochondrion; Reclinomonas americana has retained more (67) mitochondrial protein genes than other organisms; animals seem to have stabilised at 13 protein and 22 tRNA genes.