The Role of Mitochondria in Reactive Oxygen Species Generation and Its Implications for Neurodegenerative Diseases

Kausar, Saima; Wang, Feng; Cui, Hongjuan

doi:10.3390/cells7120274

Cited by 217 publications

(146 citation statements)

References 137 publications

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…Mitochondria are the major source of ROS generation [9]. In an organism, mitochondria utilize approximately 98% of the total amount of inhaled O 2 , including 1-2% for ROS generation [59,60]. Mitochondria actually produce ROS in a number of enzymatic reactions; the vast majority of the free radicals from the mitochondria are formed in the ETC during OXPHOS [61].…”

Section: Mitochondrial Ros Production and Antioxidant Enzymesmentioning

confidence: 99%

Physiological Functions of Mitochondrial Reactive Oxygen Species

Choi¹,

Kim²

2020

Free Radical Medicine and Biology

View full text Add to dashboard Cite

Mitochondria are the major energy producers within a cell in the form of adenosine triphosphate by oxidative phosphorylation. Normal mitochondrial metabolism inevitably generates reactive oxygen species (ROS), which have been considered to solely cause cellular damage. Increase of oxidative stress has been linked to various pathologies. Thus, mitochondrial ROS (mROS) were basically proposed as byproducts of oxidative metabolism, which undergo normalized by antioxidant enzymes. However, the mROS have extensively been esteemed to function as signalling molecules to regulate a wide variety of physiology. These phenomena are indeed dependent on mitochondrial redox status, which is dynamically altered under different physiological and pathological conditions. The oxidative stress is incurred by which the redox status is inclined to exceeded oxidation or reduction. Here, we attempt to integrate the recent advances in our understanding of the physiological functions of mROS.Keywords: mitochondrial ROS, oxidative stress, oxidative metabolism, redox signaling, mitochondrial physiology Free Radical Medicine and Biology 2 reactive metabolites of O 2 , including superoxide anion (O 2 ·− ) and hydrogen peroxide (H 2 O 2 ), formed by one-and two-electron reductions of O 2 , respectively [7].In the presence of transition metal ions, the more reactive hydroxyl radical (OH · ) is formed. The O 2 ·− is rapidly dismutated to H 2 O 2 by two dismutases including Cu/ Zn-superoxide dismutase (Cu/ZnSOD) in mitochondrial intermembrane space and manganese-dependent superoxide dismutase (MnSOD) in mitochondrial matrix. Unless the dismutation of O 2 ·− is catalyzed into H 2 O 2 , the radical oxidant promotes DNA damage, protein oxidation and lipid peroxidation in many types of cells. H 2 O 2 is also cell damaging molecule to be degraded to water by catalase [8]. Although the O 2 ·− generation by respiratory complexes is a well-established phenomenon, it is still poorly understood in mechanism [9].Mitochondria have been implicated in the regulation of a number of physiological and pathological processes, including proliferation, differentiation, programmed cell death, innate immunity, autophagy, redox signalling, calcium homeostasis, hypoxic stress responses and stem cell reprogramming [10][11][12][13][14][15][16]. The mROS production contributes to mitochondrial damage in a range of pathologies, which is also is closely related to redox signalling in the cell [4,17]. However, accumulating evidences show that mROS are not only deleterious molecules derived from the cellular metabolism but also indispensable participants in diverse cellular signalling and regulations [18][19][20].In this chapter, we briefly summarize recent developments in our understanding of the involvement of mROS as signalling mediators in redox biology, rather than pathological stress, underlying physiological conditions.

show abstract

Section: Mitochondrial Ros Production and Antioxidant Enzymesmentioning

confidence: 99%

Physiological Functions of Mitochondrial Reactive Oxygen Species

Choi¹,

Kim²

2020

Free Radical Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…Maintaining a population of healthy mitochondria is vital for proper development and is necessary to preserve tissue and organ function in response to stress conditions (Pickles, Vigie, & Youle, 2018). Mitochondria are well known for their importance in metabolism and energy production, but they are also a major source of reactive oxygen species (ROS), cytosolic DNA, and pro-apoptotic proteins (Kausar, Wang, & Cui, 2018;McArthur et al, 2018;Murphy, 2009;West et al, 2015). Therefore, it is important to maintain sufficient quantities of healthy mitochondria to meet current metabolic demand, but dangerous to carry an excessive surplus of these organelles.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, it is important to maintain sufficient quantities of healthy mitochondria to meet current metabolic demand, but dangerous to carry an excessive surplus of these organelles. Damaged or dysfunctional mitochondria tend to generate higher levels of ROS and cytosolic DNA compared to healthy mitochondria (Kausar et al, 2018;Murphy, 2009;Sliter et al, 2018). Exposure to high levels of ROS can cause DNA mutations in both nuclear and mitochondrial DNA and can induce protein misfolding throughout the cell (Kausar et al, 2018;Murphy, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Damaged or dysfunctional mitochondria tend to generate higher levels of ROS and cytosolic DNA compared to healthy mitochondria (Kausar et al, 2018;Murphy, 2009;Sliter et al, 2018). Exposure to high levels of ROS can cause DNA mutations in both nuclear and mitochondrial DNA and can induce protein misfolding throughout the cell (Kausar et al, 2018;Murphy, 2009). Mutations in mitochondrial DNA further decrease the health of the mitochondrial population and promote additional ROS production (Hahn & Zuryn, 2019;Mattiazzi et al, 2004;Nissanka & Moraes, 2018).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MEKK3-MEK5-ERK5 Signaling Promotes Mitochondrial Degradation

Craig

Miller

Rayavarapu

et al. 2020

Preprint

View full text Add to dashboard Cite

Mitochondria are vital organelles that coordinate cellular energy homeostasis and have important roles in cell death. Therefore, the removal of damaged or excessive mitochondria is critical for maintaining proper cellular function. The PINK1-Parkin pathway removes acutely damaged mitochondria through a well-characterized mitophagy pathway, but basal mitochondrial turnover occurs via distinct and less well-understood mechanisms. Here we report that the MEKK3-MEK5-ERK5 kinase cascade is required for mitochondrial degradation in the absence of exogenous damage. We demonstrate that genetic or pharmacological inhibition of the MEKK3-MEK5-ERK5 pathway increases mitochondrial content by reducing lysosome-mediated degradation of mitochondria under basal conditions. We show that the MEKK3-MEK5-ERK5 pathway plays a selective role in basal mitochondrial degradation but is not required for non-selective bulk autophagy, damage-induced mitophagy, or restraint of mitochondrial biogenesis. This illuminates the MEKK3-MEK5-ERK5 pathway as a positive regulator of mitochondrial degradation that acts independently of exogenous mitochondrial stressors.

show abstract

“…6,7 Mitochondria are double-membrane organelles exited in the cytoplasm of eukaryotic cells function as the power plant for the cell. 8 Mitochondria produce the energy necessary for | 537 LIU et aL. basic cellular functions in the form of adenosine triphosphate (ATP).…”

Section: Introductionmentioning

confidence: 99%

Effect of trehalose on manganese‐induced mitochondrial dysfunction and neuronal cell damage in mice

Liu

Jing

Liu

et al. 2019

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Chronic overexposure to manganese (Mn) has been verified to induce mitochondrial dysfunction, which is related to oxidative damage. The autophagic‐lysosomal degradation pathway plays a vital role in the removal of impaired mitochondria through a specific quality control mechanism termed mitophagy. However, trehalose functions as an inducer of autophagy by an mTOR‐independent mechanism, and little data report its effect on Mn‐induced mitochondrial dysfunction. To explore the possibility that trehalose could be effective in interfering with the Mn‐induced mitochondrial dysfunction, we used trehalose (2% and 4% (g/vol (mL))) in a mouse model of manganism. Our data showed that mice developed weary motor and behavioural deficits after exposure to Mn for 6 weeks. Overexposure to Mn resulted in mitochondrial dysfunction and neuronal cell damage in the basal nuclei of mice, which could be ameliorated by trehalose pre‐treatment. Moreover, our results indicated that trehalose pre‐treatment significantly reduced the oxidative damage and enhanced the activation of mitophagy. The findings clearly demonstrated that trehalose could relieve Mn‐induced mitochondrial and neuronal cell damage through its antioxidative and mitophagy‐inducing effects.

show abstract

The Role of Mitochondria in Reactive Oxygen Species Generation and Its Implications for Neurodegenerative Diseases

Cited by 217 publications

References 137 publications

Physiological Functions of Mitochondrial Reactive Oxygen Species

Physiological Functions of Mitochondrial Reactive Oxygen Species

MEKK3-MEK5-ERK5 Signaling Promotes Mitochondrial Degradation

Effect of trehalose on manganese‐induced mitochondrial dysfunction and neuronal cell damage in mice

Contact Info

Product

Resources

About