The Mitochondrial Unfolded Protein Response: A Hinge Between Healthy and Pathological Aging

Muñoz-Carvajal, Francisco; Sanhueza, Mario

doi:10.3389/fnagi.2020.581849

Cited by 42 publications

(35 citation statements)

References 98 publications

(133 reference statements)

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“…In humans, mtDNA damage has been confirmed in atherosclerotic diseases, and may be attributed to the damage of this DNA by ROS produced by the adjacent respiratory chains ( Muñoz-Carvajal and Sanhueza, 2020 ; Figure 2A ). As such, mitochondria are the site of activation of the NRLP3 inflammasome.…”

Section: Novel Mechanistic Insights: From Mitochondrial Dynamics To Atherosclerosismentioning

confidence: 99%

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Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

Yang

Xing

et al. 2021

Front. Cell Dev. Biol.

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Cardiovascular disease (CVD) is the main cause of death worldwide. Atherosclerosis is the underlying pathological basis of CVD. Mitochondrial homeostasis is maintained through the dynamic processes of fusion and fission. Mitochondria are involved in many cellular processes, such as steroid biosynthesis, calcium homeostasis, immune cell activation, redox signaling, apoptosis, and inflammation, among others. Under stress conditions, mitochondrial dynamics, mitochondrial cristae remodeling, and mitochondrial ROS (mitoROS) production increase, mitochondrial membrane potential (MMP) decreases, calcium homeostasis is imbalanced, and mitochondrial permeability transition pore open (mPTP) and release of mitochondrial DNA (mtDNA) are activated. mtDNA recognized by TLR9 can lead to NF-κB pathway activation and pro-inflammatory factor expression. At the same time, TLR9 can also activate NLRP3 inflammasomes and release interleukin, an event that eventually leads to tissue damage and inflammatory responses. In addition, mitochondrial dysfunction may amplify the activation of NLRP3 through the production of mitochondrial ROS, which together aggravate accumulating mitochondrial damage. In addition, mtDNA defects or gene mutation can lead to mitochondrial oxidative stress. Finally, obesity, diabetes, hypertension and aging are risk factors for the progression of CVD, which are closely related to mitochondrial dynamics. Mitochondrial dynamics may represent a new target in the treatment of atherosclerosis. Antioxidants, mitochondrial inhibitors, and various new therapies to correct mitochondrial dysfunction represent a few directions for future research on therapeutic intervention and amelioration of atherosclerosis.

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Section: Novel Mechanistic Insights: From Mitochondrial Dynamics To Atherosclerosismentioning

confidence: 99%

“…Cardiac fibroblasts also express STAT3. In cardiac fibroblasts, STAT3 activation promotes cardiac fibroblast proliferation (Haghikia et al, 2014) and hyaluronic acid accumulation during wound healing after acute myocardial infarction (Müller et al, 2014).…”

Section: Mitochondria-related Fibrosis and Hypertrophy In Atherosclerosismentioning

confidence: 99%

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

Yang

Xing

et al. 2021

Front. Cell Dev. Biol.

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“…At the organelle level, damage activates mitochondrial biogenesis (de novo synthesis of mitochondria), mitochondrial dynamics and mitophagy [22][23][24][25]. To preserve mitochondria from ROS-damage at DNA and protein level, antioxidant enzymes, DNA repair mechanisms, protein folding, proteases and UPRMT are active [26,27].…”

Section: The Mitochondrial Quality Control Systemmentioning

confidence: 99%

Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer

Cormio

Sanguedolce

Pesce

et al. 2021

IJMS

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Caseinolytic protease P (ClpP) is a mitochondrial serine protease. In mammalian cells, the heterodimerization of ClpP and its AAA+ ClpX chaperone results in a complex called ClpXP, which has a relevant role in protein homeostasis and in maintaining mitochondrial functionality through the degradation of mitochondrial misfolded or damaged proteins. Recent studies demonstrate that ClpP is upregulated in primary and metastatic human tumors, supports tumor cell proliferation, and its overexpression desensitizes cells to cisplatin. Interestingly, small modulators of ClpP activity, both activators and inhibitors, are able to impair oxidative phosphorylation in cancer cells and to induce apoptosis. This review provides an overview of the role of ClpP in regulating mitochondrial functionality, in supporting tumor cell proliferation and cisplatin resistance; finally, we discuss whether this protease could represent a new prognostic marker and therapeutic target for the treatment of cancer.

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“…Secondly, the combination of a decrease of energy supply and a decrease of clearance of damaged organelles could contribute to the triggering of tau pathology in aging. For example, the accumulation of dysfunctional mitochondria could restraint the supply of energy in aged cells ( 147 ). The inhibitors of the mitochondrial complex I, rotenone and annonacin, were shown to induce tau pathology in rat striatal neurons and glial cells indicating that mitochondrial dysfunction in aging could favor tau pathology ( 148 , 149 ).…”

Section: Section (Iii) Implications Of Similarities and Differences Imentioning

confidence: 99%

Similarities and Differences in the Pattern of Tau Hyperphosphorylation in Physiological and Pathological Conditions: Impacts on the Elaboration of Therapies to Prevent Tau Pathology

et al. 2021

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Tau protein, a neuronal microtubule-associated protein, becomes hyperphosphorylated in several neurodegenerative diseases called tauopathies. Hyperphosphorylation of tau is correlated to its redistribution from the axon to the somato-dendritic compartment at early stages of tauopathies. Interestingly, tau hyperphosphorylation begins in different regions of the brain in each tauopathy. In some regions, both neurons and glial cells develop tau hyperphosphorylation. Tau hyperphosphorylation is also observed in physiological conditions such as hibernation and brain development. In the first section of present article, we will review the spatiotemporal and cellular distribution of hyperphosphorylated tau in the most frequent tauopathies. In the second section, we will compare the pattern of tau hyperphosphorylation in physiological and pathological conditions and discuss the sites that could play a pivotal role in the conversion of non-toxic to toxic forms of hyperphosphorylated tau. Furthermore, we will discuss the role of hyperphosphorylated tau in physiological and pathological conditions and the fact that tau hyperphosphorylation is reversible in physiological conditions but not in a pathological ones. In the third section, we will speculate how the differences and similarities between hyperphosphorylated tau in physiological and pathological conditions could impact the elaboration of therapies to prevent tau pathology. In the fourth section, the different therapeutic approaches using tau as a direct or indirect therapeutic target will be presented.

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The Mitochondrial Unfolded Protein Response: A Hinge Between Healthy and Pathological Aging

Cited by 42 publications

References 98 publications

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer

Similarities and Differences in the Pattern of Tau Hyperphosphorylation in Physiological and Pathological Conditions: Impacts on the Elaboration of Therapies to Prevent Tau Pathology

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