Current and Emerging Therapies for Mitochondriopathies.
1Institute for Inborn Errors of Metabolism and Department of Paediatrics, Paracelsus Medical University, Salzburg, Austria. florian.lagler@pmu.ac.at.
Handbook of Experimental Pharmacology
|October 20, 2019
Summary
Mitochondrial diseases stem from genetic defects affecting cellular energy production. Current treatments are limited, highlighting the urgent need for effective therapies for these complex disorders.
Area of Science:
- Biochemistry
- Genetics
- Cell Biology
Background:
- Mitochondrial diseases are diverse genetic disorders impacting cellular respiration.
- These conditions arise from genetic variants affecting mitochondrial proteins and energy production.
- Despite progress, effective therapeutic options for mitochondrial diseases remain elusive.
Purpose of the Study:
- To review the current landscape of therapeutic strategies for mitochondrial diseases.
- To highlight the unmet need for advanced treatments.
- To discuss the potential of various therapeutic approaches.
Main Methods:
- Literature review of existing and emerging therapies for mitochondrial dysfunction.
- Analysis of therapeutic strategies targeting the electron transport chain and oxidative phosphorylation.
- Synthesis of information on antioxidant, biogenesis, and gene therapy approaches.
Main Results:
- A wide array of therapeutic strategies are being explored, including antioxidants, mitochondrial biogenesis inducers, and gene therapy.
- Current interventions show promise but have not yet yielded satisfactory clinical outcomes.
- Significant challenges persist in developing effective treatments for the heterogeneous nature of these diseases.
Conclusions:
- Mitochondrial diseases represent a significant therapeutic challenge due to their genetic and clinical heterogeneity.
- While numerous therapeutic avenues are under investigation, none are currently considered satisfactory.
- Further research and development are crucial to address the unmet medical needs in mitochondrial disease treatment.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
18.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
18.3K
01:45Mitochondrial Membranes
16.5K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
16.5K
01:39Mitochondrial Precursor Proteins
3.5K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
3.5K
01:37Mitochondria
19.4K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
19.4K
01:19Translocation of Proteins into the Mitochondria
11.8K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
11.8K
01:28The Inner Mitochondrial Membrane
4.4K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
4.4K