The neuron is high-energy utilizing tissue. The rate of neuronal cell respiration is higher than in other cells. Cellular respiration occurs with mitochondria. The healthy production and functions of mitochondria play a key role in the maintenance of healthy neurons. In pathological conditions such as neurodegenerative diseases, healthy mitochondria help to alleviate pathological events in neuronal cells. Conversely, mitochondrial dysfunction promotes the acceleration of the neurodegenerative process. Furthermore, glial-derived mitochondria contribute to multiple roles in the regulation of healthy neuron functions. It also supports releasing of the neurotransmitters; generation of the impulses, regulation of the membrane potential and molecular dynamics; controlling of the axonal transport; controlling of the mitochondrial fission and fusion functions in the peripheral as well as the central nervous system. Moreover, it plays a key role in the regeneration process of neuronal cells. Therefore, healthy mitochondria can provide a healthy environment for neuronal cell function and can treat neurodegenerative disorders. In this review, we explore the current view of healthy mitochondria and their role in healthy neuronal functions.
The past decade has witnessed a number of exciting developments in the field of mitochondrial dynamics - a phenomenon in which changes in mitochondrial shape and movement impact on cellular physiology and pathology. By undergoing fusion and fission, mitochondria are able to change their morphology between elongated interconnected networks and discrete fragmented structures, respectively. The cardiac mitochondria, in particular, have garnered much interest due to their unique spatial arrangement in the adult cardiomyocyte, and the multiple roles they play in cell death and survival. In this article, we review the role of the mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease.
Acute myocardial infarction (AMI) and the heart failure (HF) that often follows are among the leading causes of death and disability worldwide. As such novel therapies are needed to reduce myocardial infarct (MI) size, and preserve left ventricular (LV) systolic function in order to reduce the propensity for HF following AMI. Mitochondria are dynamic organelles that can undergo morphological changes by two opposing processes, mitochondrial fusion and fission. Changes in mitochondrial morphology and turnover are a vital part of maintaining mitochondrial health, DNA stability, energy production, calcium homeostasis, cellular division, and differentiation, and disturbances in the balance of fusion and fission can predispose to mitochondrial dysfunction and cell death. Changes in mitochondrial morphology are governed by mitochondrial fusion proteins (Mfn1, Mfn2 and OPA1) and mitochondrial fission proteins (Drp1, hFis1, and Mff). Recent experimental data suggest that mitochondria undergo fission during acute ischemia/reperfusion injury (IRI), generating fragmented dysfunctional mitochondrial and predisposing to cell death. We and others have shown that genetic and pharmacological inhibition of the mitochondrial fission protein Drp1 can protect cardiomyocytes from acute IRI and reduce MI size. Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and mitochondrial dynamics proteins of 51 kDa (MiD51), have been recently described, which have been shown to mediating mitochondrial fission by targeting Drp1 to the mitochondrial surface. In this review article, we provide an overview of MiD49 and MiD51, and highlight their potential as novel therapeutic targets for treating cardiovascular diseases such as AMI, anthracycline cardiomyopathy, and pulmonary arterial hypertension.