Mitochondrial Dynamics: Molecular Mechanisms, Related Primary Mitochondrial Disorders and Therapeutic Approaches

Abstract

Mitochondria do not exist as individual entities in the cell—conversely, they constitute an interconnected community governed by the constant and opposite process of fission and fusion. The mitochondrial fission leads to the formation of smaller mitochondria, promoting the biogenesis of new organelles. On the other hand, following the fusion process, mitochondria appear as longer and interconnected tubules, which enhance the communication with other organelles. Both fission and fusion are carried out by a small number of highly conserved guanosine triphosphatase proteins and their interactors. Disruption of this equilibrium has been associated with several pathological conditions, ranging from cancer to neurodegeneration, and mutations in genes involved in mitochondrial fission and fusion have been reported to be the cause of a subset of neurogenetic disorders.

Identifying The Prognostic Significance of Mitochondrial AAA Proteases YME1L1 Expression in Ovarian Cancer

“…In addition, mitochondria are responsible for cell metabolism, differentiation and apoptosis by regulating redox reactions, amino acid and lipid metabolism, reactive oxygen species (ROS) production, calcium homeostasis and mitochondrial permeability transition pore (mPTP) (21,22). Mitochondrial dysfunction is closely related to tumorigenesis, growth, invasion and metastasis (23). Mitochondria are capable of performing a series of biologically precise functions with specialized molecular partners, the mitochondrial unfolded protein response (mtUPR) and processing peptidases that facilitate proper protein folding and complex assembly.…”

Mitochondrial Neurodegeneration

“…This is a fatal condition, variably combining neurological signs (hypotonia, hyporeflexia, and floppiness), with respiratory muscle insufficiency, and in some subjects, hypertrophic cardiomyopathy. Likewise, de novo heterozygous mutations can affect DNM1L , encoding a protein with a major role in mitochondrial fission, usually associated with severe, infantile encephalopathy, whereas transmissible, recessive DNM1L mutations cause a form of optic atrophy (OA5) (OMIM *603850) [ 176 ]. Incidentally, an expanding number of mutations involve other genes associated with mitochondrial dynamics, such as MFN2 , encoding mitofusin 2, promoting fusion of the mitochondrial outer membrane, heterozygous mutations of which are responsible for CMT2B (OMIM 608507) or OPA1, a gene responsible for autosomal dominant optic atrophy type 1 (ADOA1), but also of a syndromic form of dominant optic atrophy with encephalopathic PEO and multiple mtDNA deletions (OMIM *605290) [ 176 ].…”

Mitochondrial Implications in Cardiovascular Aging and Diseases: The Specific Role of Mitochondrial Dynamics and Shifts

“…During the process of mitochondrial fusion, both of the mitochondrial membranes of the consolidating organelles merge (see Figure 1 ). This process is controlled by a range of proteins, such as mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy protein 1 (Opa1), all of which belong to the dynamin-related GTPases family [ 8 ]. The fusion of OMM is mediated by mitofusins 1 and 2, while the fusion of the inner mitochondrial membranes requires the presence of optic atrophy protein 1.…”