Detoxification mechanisms of ginseng to aconite: A review

The mitochondrion is at the core of cellular energy metabolism, being the site of most ATP generation. Calcium is a key regulator of mitochondrial function and acts at several levels within the organelle to stimulate ATP synthesis. However, the dysregulation of mitochondrial Ca(2+) homeostasis is now recognized to play a key role in several pathologies. For example, mitochondrial matrix Ca(2+) overload can lead to enhanced generation of reactive oxygen species, triggering of the permeability transition pore, and cytochrome c release, leading to apoptosis. Despite progress regarding the independent roles of both Ca(2+) and mitochondrial dysfunction in disease, the molecular mechanisms by which Ca(2+) can elicit mitochondrial dysfunction remain elusive. This review highlights the delicate balance between the positive and negative effects of Ca(2+) and the signaling events that perturb this balance. Overall, a "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction.

Mitochondrial damage is a critical contributor to cardiac ischemia/reperfusion (I/R) injury. Mitochondrial quality control (MQC) mechanisms, a series of adaptive responses that preserve mitochondrial structure and function, ensure cardiomyocyte survival and cardiac function after I/R injury. MQC includes mitochondrial fission, mitochondrial fusion, mitophagy and mitochondria-dependent cell death. The interplay among these responses is linked to pathological changes such as redox imbalance, calcium overload, energy metabolism disorder, signal transduction arrest, the mitochondrial unfolded protein response and endoplasmic reticulum stress. Excessive mitochondrial fission is an early marker of mitochondrial damage and cardiomyocyte death. Reduced mitochondrial fusion has been observed in stressed cardiomyocytes and correlates with mitochondrial dysfunction and cardiac depression. Mitophagy allows autophagosomes to selectively degrade poorly structured mitochondria, thus maintaining mitochondrial network fitness. Nevertheless, abnormal mitophagy is maladaptive and has been linked to cell death. Although mitochondria serve as the fuel source of the heart by continuously producing adenosine triphosphate, they also stimulate cardiomyocyte death by inducing apoptosis or necroptosis in the reperfused myocardium. Therefore, defects in MQC may determine the fate of cardiomyocytes. In this review, we summarize the regulatory mechanisms and pathological effects of MQC in myocardial I/R injury, highlighting potential targets for the clinical management of reperfusion.

Almost 30 years ago it was first appreciated that anti-apoptotic B-cell lymphoma-2 (BCL-2) prevents the induction of apoptosis not only in malignant cells, but also in normal cellular lineages. This critical observation has rapidly evolved from merely identifying new BCL-2 family members to understanding how their biochemical interactions trigger the cell death process, and, more recently, to pharmacological inhibition of anti-apoptotic BCL-2 function in disease. Indeed, the proper regulation of apoptosis is important in many aspects of life including development, homeostasis, and disease biology. To better understand these processes, scientists have used many tools to assess the contribution of individual anti-apoptotic BCL-2 family members. This review will focus on the prominent roles for BCL-2 and other pro-survival family members in promoting the development of mammals during early embryogenesis, neurogenesis, and hematopoiesis.