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Mitochondria are double-membrane organelles within eukaryotic cells that act as cellular power houses owing to their ability to efficiently generate the ATP required to sustain normal cell function. Also, they represent a "hub" for the regulation of a plethora of processes, including cellular homeostasis, metabolism, the defense against oxidative stress, and cell death. Mitochondrial dysfunctions are associated with a wide range of human diseases with complex pathologies, including metabolic diseases, neurodegenerative disorders, and cancer. Therefore, regulating dysfunctional mitochondria represents a pivotal therapeutic opportunity in biomedicine. Marine ecosystems are biologically very diversified and harbor a broad range of organisms, providing both novel bioactive substances and molecules with meaningful biomedical and pharmacological applications. Recently, many mitochondria-targeting marine-derived molecules have been described to regulate mitochondrial biology, thus exerting therapeutic effects by inhibiting mitochondrial abnormalities, both in vitro and in vivo, through different mechanisms of action. Here, we review different strategies that are derived from marine organisms which modulate specific mitochondrial processes or mitochondrial molecular pathways and ultimately aim to find key molecules to treat a wide range of human diseases characterized by impaired mitochondrial function. [ABSTRACT FROM AUTHOR]

The cerebrospinal fluid (CSF) is a waterly, colorless fluid contained within the brain ventricles and the cranial and spinal subarachnoid spaces. CSF physiological functions range from hydromechanical protection of the central nervous system (CNS) to CNS modulation of developmental processes and regulation of interstitial fluid homeostasis. Optic nerve (ON) is surrounded by CSF circulating in the subarachnoid spaces and is exposed to both CSF (CSFP) and intra ocular (IOP) pressures, which converge at the lamina cribrosa (LC) as two opposite forces. The trans–lamina cribrosa pressure gradient (TLPG) is defined as IOP - CSFP and its alterations (due either to an elevation in IOP or a reduction in ICP) could result in structural damaging of the ON, including glaucomatous changes. The purpose of this review is to update the readers on the CSF contribution in controlling the functions/dysfunctions of ON by regulating homeostasis at LC. We also highlight emerging parallelisms regarding the expression of cilia-related genes in the regulation of common functions of body fluids in both brain and eye structures. [ABSTRACT FROM AUTHOR]

3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”) is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMA-associated disruption of Ca2+ homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increased mitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of “ecstasy”-induced neuronal injury. [ABSTRACT FROM PUBLISHER]