Mitohormesis; Potential implications in neurodegenerative diseases
Section snippets
Mitochondrial dysfunction and neurodegeneration
Neurodegenerative diseases (NDDs) includes spectrum of disorders characterized by progressive loss of neurons in central and peripheral nervous system (Ellis and Fell, 2017, Jellinger, 2010, Hoogendam, 2017). These include range of neuronal pathologies where PD and AD are most prevalent affecting 8% population worldwide increasing socioeconomic burden of society (Association, 2019). Other NDDs such as multiple sclerosis (MS), Huntingtońs disease (HD), amyotrophic lateral sclerosis (ALS),
ROS levels in neuronal pathologies
Oxidative stress observed in various neuronal pathologies is due to excess of reactive oxygen species (ROS) which leads to persistent or reversible cellular damage (Singh et al., 2019, Tönnies and Trushina, 2017, Gandhi and Abramov, 2012.). The majority of existing molecular mechanism for oxidative stress suggest imbalance between levels of oxidants and antioxidants (Singh et al., 2019). Brain is the organelle which is highly metabolically active and is more vulnerable to oxidative stress (
Mitohormesis: ROS as an important signaling molecule
ROS are generally considered to have short life and consist of highly reactive radicals, peroxides, radical anions, and combinations of them, including singlet oxygen (1O2), superoxide radical anion (O2•–), hydrogen peroxide (H2O2), hydroperoxyl radical (HO2•), hydroxyl radical (OH•), hydroxyl anion (OH–), peroxide radical anion (•O22–), peroxyl radicals (RO2 •) and others (Hoogendam, 2017, Bolisetty and Jaimes, 2013)). As ROS are highly reactive, they quickly react with biological molecules
Nuclear-mitochondrial crosstalk
A typical human cell is comprised of multiple subcellular compartments which are membrane bound organelles. Though each organelle has been viewed as individual entities and allotted specific functions, it still requires extensive inter organelle communication to maintain normal cellular operation (Shai, et al., 2018, Valm, 2017, Keenan et al., 2020). This communication mostly requires contact sites for this purpose, or it can be relay of signals by means intermediates (Höglinger, 2019,
Nuclear encoded miRNAs translocate to mitochondria: Possible role in mitohormesis
The transport of nuclear encoded RNAs to mitochondria is one of the mechanisms which regulate mitochondrial capacity in different patho-physiological conditions (Jeandard et al., 2019, Kamenski et al., 2019, Abbott et al., 2014). Interestingly small noncoding RNAs including miRNAs have been shown to translocate to mitochondria; however, the role of these miRNAs in various stress conditions have not been investigated yet. miRNAs belong to family of small noncoding RNAs, which play an important
Mitohormesis benefits neurons
Although mitohormesis have not been studied extensively in different disease models, there are few reports which suggest the role mitohormesis in tumor cell survival and promoting metastasis under cancerous condition (Bao, 2015, Kenny, 2019) . This recent report showed that mitohormesis primes a subpopulation of cancer cells to basally upregulate mitochondrial stress responses, which include the mitochondrial unfolded protein response(UPRmt) providing an adaptive metastatic advantage (Kenny,
Concluding remarks
The maintenance of healthy brain and prevention/delay of neurodegeneration have been the goal for ageing research. Several studies from the last decade have shown role of mitochondrial ROS in neurodegeneration and its impact on aging, which led to development and establishment of free radical theory of ageing (FRTA) (Yun and Finkel, 2014). According to FRTA, ageing and neurodegeneration are primarily caused by mitochondrial mediated generation of ROS (Lagouge and Larsson, 2013, Stefanatos and
CRediT authorship contribution statement
Dhruv Gohel: Conceptualization, Methodology, Writing - original draft. Rajesh Singh: Supervision, Conceptualization, Writing - review & editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
The research for mitochondrial involvement in NDDs was financially supported by multiple funding agencies including Department of Science and Technology (DST, India), Department of Biotechnology (DBT, India), Indian Council of Medical Research (ICMR) and SERB (Science and Engineering Research Board, India) to Prof. Rajesh Singh. Dhruv Gohel has received Senior Research Fellowship (Ref No: 3/1/2/126/Neuro/2019-NCD-1) from Indian Council of Medical Research (ICMR). Authors also acknowledge the
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