Mitochondria are primarily responsible for providing the contracting cardiac myocyte with a continuous supply of ATP. However, mitochondria can rapidly change into death-promoting organelles. In response to changes in the intracellular environment, mitochondria become producers of excessive reactive oxygen species and release prodeath proteins, resulting in disrupted ATP synthesis and activation of cell death pathways. Interestingly, cells have developed a defense mechanism against aberrant mitochondria that can cause harm to the cell. This mechanism involves selective sequestration and subsequent degradation of the dysfunctional mitochondrion before it causes activation of cell death. Induction of mitochondrial autophagy, or mitophagy, results in selective clearance of damaged mitochondria in cells. In response to stress such as ischemia/reperfusion, prosurvival and prodeath pathways are concomitantly activated in cardiac myocytes. Thus, there is a delicate balance between life and death in the myocytes during stress, and the final outcome depends on the complex cross-talk between these pathways. Mitophagy functions as an early cardioprotective response, favoring adaptation to stress by removing damaged mitochondria. In contrast, increased oxidative stress and apoptotic proteases can inactivate mitophagy, allowing for the execution of cell death. Herein, we discuss the importance of mitochondria and mitophagy in cardiovascular health and disease and provide a review of our current understanding of how these processes are regulated.
"Induction of ROS levels stimulates autophagy and mitophagy as exemplified by lower mtDNA content in placental tissue (Kubli and Gustafsson 2012). In the current study, stratified analyses indicated a stronger inverse association between placental mtDNA content and prenatal NO 2 exposure in newborn boys than in girls. "
[Show abstract][Hide abstract] ABSTRACT: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction.
We investigated whether placental mtDNA content is a possible mediator of the association between prenatal NO2 exposure and birth weight.
We used data from two independent European cohorts: INMA (n=376; Spain) and ENVIRONAGE (n=550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled dataset were calculated using multiple linear regression and mixed models. We also performed a mediation analysis.
Pooled estimates indicated that a 10µg/m(3) increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% confidence interval (CI): -9.3, -0.3%). and a 48g decrease (95% CI: -87, -9g) in birth weight. However, the association with birth weight was significant for INMA (-66g; 95% CI: -111, -23g) but not for ENVIRONAGE (-20g; 95% CI: -101, 62g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, IQR increase: 140g; 95% CI: 43, 237g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content.
Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight.
Environmental Health Perspectives 08/2015; DOI:10.1289/ehp.1408981 · 7.98 Impact Factor
"Other perturbations can lead to single, condensed mitochondrial structures. In stress situations, such as changes in the availability of nutrients or exposure to mitochondrial damaging agents (Rafelski, 2013), loss of the MMP leads to fission of the mitochondrial network into smaller units, which facilitates the protection of mitochondria, or when damage is excessive, their degradation by the process of mitophagy (Breitenbach et al., 2014; Kubli and Gustafsson, 2012). As MMP and mitochondrial fragmentation status are not necessarily coupled to each other (Bajić et al., 2013; Konno and Kako, 1991), both parameters need to measured in order to evaluate the physiological status of mitochondrial functionality. "
"Apoptosis, also called programmed cell death, plays a critical role in many biological processes including development, maintenance of homeostasis and immune defense  . Apoptosis is a complex and highly regulated cellular process and the delicate balance between the pro-and anti-apoptotic mechanisms determines whether a cell will commit suicide or live when a cell is under stress and the cell death signal is activated  . Apoptosis is usually divided into two pathways: the intrinsic or mitochondrial pathway and the extrinsic or death receptor pathway . "
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