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Cited by 264Autophagy in Disease and TherapyParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

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Mitochondrial and lysosomal biogenesis are activated following PINK 1/parkin‐mediated mitophagy

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Ivankovic, Davor, Chau, Kai‐Yin, Schapira, Anthony H. V., Gegg, Matthew E.·2016·Journal of Neurochemistry
DOI 10.1111/jnc.13412PMC PMC4949652
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Abstract

Impairment of the autophagy-lysosome pathway is implicated with the changes in α-synuclein and mitochondrial dysfunction observed in Parkinson's disease (PD). Damaged mitochondria accumulate PINK1, which then recruits parkin, resulting in ubiquitination of mitochondrial proteins. These can then be bound by the autophagic proteins p62/SQSTM1 and LC3, resulting in degradation of mitochondria by mitophagy. Mutations in PINK1 and parkin genes are a cause of familial PD. We found a significant increase in the expression of p62/SQSTM1 mRNA and protein following mitophagy induction in human neuroblastoma SH-SY5Y cells. p62 protein not only accumulated on mitochondria, but was also greatly increased in the cytosol. Increased p62/SQSMT1 expression was prevented in PINK1 knock-down cells, suggesting increased p62 expression was a consequence of mitophagy induction. The transcription factors Nrf2 and TFEB, which play roles in mitochondrial and lysosomal biogenesis, respectively, can regulate p62/SQSMT1. We report that both Nrf2 and TFEB translocate to the nucleus following mitophagy induction and that the increase in p62 mRNA levels was significantly impaired in cells with Nrf2 or TFEB knockdown. TFEB translocation also increased expression of itself and lysosomal proteins such as glucocerebrosidase and cathepsin D following mitophagy induction. We also report that cells with increased TFEB protein have significantly higher PGC-1α mRNA levels, a regulator of mitochondrial biogenesis, resulting in increased mitochondrial content. Our data suggests that TFEB is activated following mitophagy to maintain autophagy-lysosome pathway and mitochondrial biogenesis. Therefore, strategies to increase TFEB may improve both the clearance of α-synuclein and mitochondrial dysfunction in PD. Damaged mitochondria are degraded by the autophagy-lysosome pathway and is termed mitophagy. Following mitophagy induction, the transcription factors Nrf2 and TFEB translocate to the nucleus, inducing the transcription of genes encoding for autophagic proteins such as p62, as well as lysosomal and mitochondrial proteins. We propose that these events maintain autophagic flux, replenish lysosomes and replace mitochondria.

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Figure 1 p62 protein expression is increased following carbonyl cyanide m‐chlorophenylhydrazone (CCCP) treatment. (a) SH‐SY5Y cells were treated with 10 μM CCCP for 6 or 18 h and p62 (green) and the mitochondrial protein TOM20 (red) were detected by immunofluorescence. Nuclei were counter‐stained with 4′,6‐diamidino‐2‐phenylindole (blue) (b) SH‐SY5Y cells were treated with 10 μM CCP for 18 h, homogenised and cytosolic and mitochondrial enriched fractions prepared. Fractions (20 μg protein) were analysed by western blot for p62 protein. Fractions were also probed for the mitochondrial protein cytochrome oxidase (COX) subunit IV and the cytosolic marker β‐tubulin. (c) SH‐SY5Y cells were treated with 10 μM CCCP and p62 mRNA levels measured by qPCR (n = 7) or (d) p62 protein levels by western blotting (n = 6). *p < 0.05 versus 0 h; **p < 0.01 versus 0 h.
Figure 1 p62 protein expression is increased following carbonyl cyanide m‐chlorophenylhydrazone (CCCP) treatment. (a) SH‐SY5Y cells were treated with 10 μM CCCP for 6 or 18 h and p62 (green) and the mitochondrial protein TOM20 (red) were detected by immunofluorescence. Nuclei were counter‐stained with 4′,6‐diamidino‐2‐phenylindole (blue) (b) SH‐SY5Y cells were treated with 10 μM CCP for 18 h, homogenised and cytosolic and mitochondrial enriched fractions prepared. Fractions (20 μg protein) were analysed by western blot for p62 protein. Fractions were also probed for the mitochondrial protein cytochrome oxidase (COX) subunit IV and the cytosolic marker β‐tubulin. (c) SH‐SY5Y cells were treated with 10 μM CCCP and p62 mRNA levels measured by qPCR (n = 7) or (d) p62 protein levels by western blotting (n = 6). *p < 0.05 versus 0 h; **p < 0.01 versus 0 h.CC BY · PubMed Central
Figure 2 Macroautophagy flux is increased and mitochondrial content decreased following carbonyl cyanide m‐chlorophenylhydrazone (CCCP) treatment. (a) SH‐SY5Y cells were treated with 10 μΜ CCCP and LC3‐II protein levels measured by western blot. The ratio of (LC3‐II/LC3‐I)/β‐actin was calculated (n = 4). (b) Macroautophagy flux was measured by treating SH‐SY5Y cells with vehicle, 10 μΜ CCCP, or 10 μΜ CCCP + 100 nM bafilomycin A1 for 6 h and LC3‐II protein levels measured by western blotting (n = 4). Data expressed as (LC3‐II/LC3‐I)/β‐actin. (c) The decrease in mitochondrial content was measured by western blot after 6, 9 or 18 h of CCCP treatment using antibodies against the mitochondrial proteins TOM20 and prohibitin 1. *p < 0.05 versus 0 h.
Figure 2 Macroautophagy flux is increased and mitochondrial content decreased following carbonyl cyanide m‐chlorophenylhydrazone (CCCP) treatment. (a) SH‐SY5Y cells were treated with 10 μΜ CCCP and LC3‐II protein levels measured by western blot. The ratio of (LC3‐II/LC3‐I)/β‐actin was calculated (n = 4). (b) Macroautophagy flux was measured by treating SH‐SY5Y cells with vehicle, 10 μΜ CCCP, or 10 μΜ CCCP + 100 nM bafilomycin A1 for 6 h and LC3‐II protein levels measured by western blotting (n = 4). Data expressed as (LC3‐II/LC3‐I)/β‐actin. (c) The decrease in mitochondrial content was measured by western blot after 6, 9 or 18 h of CCCP treatment using antibodies against the mitochondrial proteins TOM20 and prohibitin 1. *p < 0.05 versus 0 h.CC BY · PubMed Central
Figure 3 Increased p62 expression is prevented in PINK1 knock‐down cells. (a) SH‐SY5Y cells expressing scrambled shRNA or PINK1 shRNA (117‐2, 118‐3, and 118‐4) were treated with 10 μM carbonyl cyanide m‐chlorophenylhydrazone (CCCP) for 24 h and full‐length (FL) PINK1 protein levels measured by western blot. No accumulation of FL PINK1 was observed in 118‐3 and 118‐4 PINK1 shRNA clones. (b) SH‐SY5Y cells constitutively expressing scrambled (scram) or PINK1 shRNA (clone 118‐3) were treated with vehicle or 10 μM CCCP for 24 h and p62 protein expression measured by western blotting. **p < 0.05 versus scram CCCP; n = 9. (c) SH‐SY5Y cells were incubated in serum‐free culture media for up to 24 h to induce starvation‐mediated macroautophagy. p62 protein levels were measured by western blotting. *p < 0.05 versus 0 h; **p < 0.01 versus 0 h; n = 4. (d) SH‐SY5Y cells were transfected with scrambled (scram) or p62 siRNA for 72 h. For the last 24 h, cells were treated with vehicle (ethanol) or 10 μM CCCP. p62 protein expression was then measured by western blotting. p62 protein was significantly decreased in p62 siRNA cells under basal conditions and following CCCP treatment, when compared to scram cells. **p < 0.01 versus scram vehicle or scram CCCP; n = 3. (e) Mitochondrial content was measured in SH‐SY5Y cells treated with scram or p62 siRNA for 72 h by measuring citrate synthase (CS) activity. For the last 24 h, cells were treated with vehicle or 10 μM CCCP and data are expressed as % of vehicle. *p < 0.05 versus scram CCCP treatment; n = 5.
Figure 3 Increased p62 expression is prevented in PINK1 knock‐down cells. (a) SH‐SY5Y cells expressing scrambled shRNA or PINK1 shRNA (117‐2, 118‐3, and 118‐4) were treated with 10 μM carbonyl cyanide m‐chlorophenylhydrazone (CCCP) for 24 h and full‐length (FL) PINK1 protein levels measured by western blot. No accumulation of FL PINK1 was observed in 118‐3 and 118‐4 PINK1 shRNA clones. (b) SH‐SY5Y cells constitutively expressing scrambled (scram) or PINK1 shRNA (clone 118‐3) were treated with vehicle or 10 μM CCCP for 24 h and p62 protein expression measured by western blotting. **p < 0.05 versus scram CCCP; n = 9. (c) SH‐SY5Y cells were incubated in serum‐free culture media for up to 24 h to induce starvation‐mediated macroautophagy. p62 protein levels were measured by western blotting. *p < 0.05 versus 0 h; **p < 0.01 versus 0 h; n = 4. (d) SH‐SY5Y cells were transfected with scrambled (scram) or p62 siRNA for 72 h. For the last 24 h, cells were treated with vehicle (ethanol) or 10 μM CCCP. p62 protein expression was then measured by western blotting. p62 protein was significantly decreased in p62 siRNA cells under basal conditions and following CCCP treatment, when compared to scram cells. **p < 0.01 versus scram vehicle or scram CCCP; n = 3. (e) Mitochondrial content was measured in SH‐SY5Y cells treated with scram or p62 siRNA for 72 h by measuring citrate synthase (CS) activity. For the last 24 h, cells were treated with vehicle or 10 μM CCCP and data are expressed as % of vehicle. *p < 0.05 versus scram CCCP treatment; n = 5.CC BY · PubMed Central
Figure 4 Nrf2 translocates to nucleus and affects p62 expression following carbonyl cyanide m‐chlorophenylhydrazone (CCCP) treatment. (a) SH‐SY5Y cells were treated with 10 μM CCCP for 18 h and Nrf2 nuclear localisation measured by immunofluorescence. Nrf2 is in green; nuclei in blue (4′,6‐diamidino‐2‐phenylindole stain). (b) Nrf2 protein levels measured by western blotting were also increased following 18 h of CCCP treatment. (c) SH‐SY5Y cells were treated with 10 μM CCCP for 18 h and cytosolic and nuclear fractions prepared. Nrf2 protein was detected in cytosolic (0.6% of total volume) and nuclear fractions (18% of total volume) by western blotting. The purity of the nuclear and cytosolic fractions was assessed by western blotting using lamin A and β‐actin antibodies respectively. (d) RNA was extracted from SH‐SY5Y cells treated with CCCP for 0–18 h and qPCR performed for NQO1 mRNA levels. Data normalised against β‐actin mRNA. **p < 0.01 versus 0 h; n = 3. (e) SH‐SY5Y cells were treated with scram or Nrf2 siRNA for 72 h. Knockdown (KD) of Nrf2 protein levels was measured by western blotting. (f) For the last 24 h, sister wells were treated with vehicle or 10 μM CCCP. RNA was extracted and p62 mRNA levels measured by qPCR. Nrf2 knockdown significantly decreased p62 mRNA levels after CCCP treatment. Data normalised against β‐actin mRNA. **p < 0.01 versus scram CCCP; n = 3.
Figure 4 Nrf2 translocates to nucleus and affects p62 expression following carbonyl cyanide m‐chlorophenylhydrazone (CCCP) treatment. (a) SH‐SY5Y cells were treated with 10 μM CCCP for 18 h and Nrf2 nuclear localisation measured by immunofluorescence. Nrf2 is in green; nuclei in blue (4′,6‐diamidino‐2‐phenylindole stain). (b) Nrf2 protein levels measured by western blotting were also increased following 18 h of CCCP treatment. (c) SH‐SY5Y cells were treated with 10 μM CCCP for 18 h and cytosolic and nuclear fractions prepared. Nrf2 protein was detected in cytosolic (0.6% of total volume) and nuclear fractions (18% of total volume) by western blotting. The purity of the nuclear and cytosolic fractions was assessed by western blotting using lamin A and β‐actin antibodies respectively. (d) RNA was extracted from SH‐SY5Y cells treated with CCCP for 0–18 h and qPCR performed for NQO1 mRNA levels. Data normalised against β‐actin mRNA. **p < 0.01 versus 0 h; n = 3. (e) SH‐SY5Y cells were treated with scram or Nrf2 siRNA for 72 h. Knockdown (KD) of Nrf2 protein levels was measured by western blotting. (f) For the last 24 h, sister wells were treated with vehicle or 10 μM CCCP. RNA was extracted and p62 mRNA levels measured by qPCR. Nrf2 knockdown significantly decreased p62 mRNA levels after CCCP treatment. Data normalised against β‐actin mRNA. **p < 0.01 versus scram CCCP; n = 3.CC BY · PubMed Central
Figure 5 TFEB translocates to the nucleus and affects p62 expression following carbonyl cyanide m‐chlorophenylhydrazone (CCCP) treatment. (a) SH‐SY5Y cells were treated with scrambled (scram) or TFEB siRNA for 72 h and TFEB protein expression measured by western blotting. **p < 0.01 versus scram; n = 4. (b) During the last 24 h of TFEB knock‐down, cells were treated with vehicle or 10 μM CCCP for 24 h and RNA extracted. p62 mRNA levels were measured by qPCR and normalised to β‐actin mRNA levels. **p < 0.01 versus scram CCCP‐treated cells; n = 4. (c) p62 protein levels were also measured following 24 h CCCP treatment of SH‐SY5Y cells treated with scram or TFEB and Nrf2 siRNA for previous 72 h. (d) Following 24 h CCCP treatment of SH‐SY5Y cells, total cell lysates were prepared and subcellular fractionation performed to generate cytosolic and nuclear fractions. TFEB protein was detected by western blotting. Lamin A and β‐actin were also measured to assess purity of the nuclear and cytosolic fractions respectively. (e) SH‐SY5Y cells were treated with CCCP for 24 h and endogenous TFEB measured in total cell lysates by western blotting. (f) SH‐SY5Y cell lines expressing exogenous TFEB with a DDK tag (clones T4 and T5) were generated. TFEB protein expression in parental SH‐SY5Y cell line and clones T4 and T5 was measured by western blotting with a TFEB antibody. Endogenous TFEB is shown by arrow. (g) TFEB‐DDK cells were treated with vehicle or CCCP for 24 h and TFEB detected by immunofluorescence with an antibody against DDK (green). Nuclei are stained blue with 4′,6‐diamidino‐2‐phenylindole. (h) Total cell lysates were prepared from SH‐SY5Y cells (SH) and TFEB‐DDK cells and p62 protein levels measured by western blotting.
Figure 5 TFEB translocates to the nucleus and affects p62 expression following carbonyl cyanide m‐chlorophenylhydrazone (CCCP) treatment. (a) SH‐SY5Y cells were treated with scrambled (scram) or TFEB siRNA for 72 h and TFEB protein expression measured by western blotting. **p < 0.01 versus scram; n = 4. (b) During the last 24 h of TFEB knock‐down, cells were treated with vehicle or 10 μM CCCP for 24 h and RNA extracted. p62 mRNA levels were measured by qPCR and normalised to β‐actin mRNA levels. **p < 0.01 versus scram CCCP‐treated cells; n = 4. (c) p62 protein levels were also measured following 24 h CCCP treatment of SH‐SY5Y cells treated with scram or TFEB and Nrf2 siRNA for previous 72 h. (d) Following 24 h CCCP treatment of SH‐SY5Y cells, total cell lysates were prepared and subcellular fractionation performed to generate cytosolic and nuclear fractions. TFEB protein was detected by western blotting. Lamin A and β‐actin were also measured to assess purity of the nuclear and cytosolic fractions respectively. (e) SH‐SY5Y cells were treated with CCCP for 24 h and endogenous TFEB measured in total cell lysates by western blotting. (f) SH‐SY5Y cell lines expressing exogenous TFEB with a DDK tag (clones T4 and T5) were generated. TFEB protein expression in parental SH‐SY5Y cell line and clones T4 and T5 was measured by western blotting with a TFEB antibody. Endogenous TFEB is shown by arrow. (g) TFEB‐DDK cells were treated with vehicle or CCCP for 24 h and TFEB detected by immunofluorescence with an antibody against DDK (green). Nuclei are stained blue with 4′,6‐diamidino‐2‐phenylindole. (h) Total cell lysates were prepared from SH‐SY5Y cells (SH) and TFEB‐DDK cells and p62 protein levels measured by western blotting.CC BY · PubMed Central
Figure 6 Lysosomal enzyme activity increased following carbonyl cyanide m‐chlorophenylhydrazone (CCCP)‐induced mitophagy. (a) TFEB‐DDK cells were treated with vehicle (black) or 10 μM CCCP (white) for 24 h and the activities of GCase (nmol/h/mg protein) and β‐hexosaminidase (HEX) (nmol/min/mg protein) were measured in cell lysates. *p < 0.05 versus vehicle; **p < 0.01 versus vehicle; n = 4. (b) SH‐SY5Y cells treated with scrambled (scram) or TFEB siRNA for 72 h. For the last 24 h cells were treated with vehicle or 10 μM CCCP and GCase activity measured in cell lysates. *p < 0.05 versus vehicle; n = 4. (c) SH‐SY5Y cells expressing scrambled (scram) shRNA or PINK1 shRNA were treated with vehicle or CCCP for 24 h. GCase and HEX enzyme activity was measured in cell lysates. *p < 0.05 versus vehicle; n = 5. (d) SH‐SY5Y cells or TFEB‐DDK cells were treated with vehicle or CCCP for 24 h and cathepsin D protein levels measured by western blotting.
Figure 6 Lysosomal enzyme activity increased following carbonyl cyanide m‐chlorophenylhydrazone (CCCP)‐induced mitophagy. (a) TFEB‐DDK cells were treated with vehicle (black) or 10 μM CCCP (white) for 24 h and the activities of GCase (nmol/h/mg protein) and β‐hexosaminidase (HEX) (nmol/min/mg protein) were measured in cell lysates. *p < 0.05 versus vehicle; **p < 0.01 versus vehicle; n = 4. (b) SH‐SY5Y cells treated with scrambled (scram) or TFEB siRNA for 72 h. For the last 24 h cells were treated with vehicle or 10 μM CCCP and GCase activity measured in cell lysates. *p < 0.05 versus vehicle; n = 4. (c) SH‐SY5Y cells expressing scrambled (scram) shRNA or PINK1 shRNA were treated with vehicle or CCCP for 24 h. GCase and HEX enzyme activity was measured in cell lysates. *p < 0.05 versus vehicle; n = 5. (d) SH‐SY5Y cells or TFEB‐DDK cells were treated with vehicle or CCCP for 24 h and cathepsin D protein levels measured by western blotting.CC BY · PubMed Central
Figure 7 Mitochondrial content and PGC‐1α levels are increased in cells with greater TFEB protein expression. (a) Mitochondrial content was measured in SH‐SY5Y cells and TFEB‐DDK cells under basal conditions by assaying citrate synthase (CS) activity. **p < 0.01 versus SH‐SY5Y; n = 6. (b) Western blotting for the mitochondrial proteins prohibitin 1 and cytochrome oxidase (COX) subunit IV also indicated that mitochondrial content was increased in TFEB‐DDK cells. (c) PGC‐1α mRNA levels were measured in SH‐SY5Y cells and TFEB‐DDK cells under basal conditions by qPCR. Data normalised against β‐actin mRNA levels. **p < 0.01 versus SH‐SY5Y cells; n = 3. (d) SH‐SY5Y cells were treated with scrambled (scram) or TFEB siRNA for 72 h and PGC‐1α mRNA levels measured. *p < 0.05 versus scram; n = 4. (e) PGC‐1α protein levels were detected by western blotting in total cell lysates of SH‐SY5Y cells, TFEB‐DDK cells and a SH‐SY5Y cell line over‐expressing human PGC‐1α. The fold increase in PGC‐1α protein density for this blot and PGC‐1α mRNA levels of the respective cell lines are reported underneath the blot. (f) TFEB‐DDK cells were treated with 10 μM carbonyl cyanide m‐chlorophenylhydrazone (CCCP) for 18 h and cytosolic and nuclear fractions prepared. PGC‐1α protein was detected in cytosolic (3.5% of total volume) and nuclear fractions (35% of total volume) by western blotting. The purity of the nuclear and cytosolic fractions was assessed by western blotting using lamin A and β‐actin antibodies respectively.
Figure 7 Mitochondrial content and PGC‐1α levels are increased in cells with greater TFEB protein expression. (a) Mitochondrial content was measured in SH‐SY5Y cells and TFEB‐DDK cells under basal conditions by assaying citrate synthase (CS) activity. **p < 0.01 versus SH‐SY5Y; n = 6. (b) Western blotting for the mitochondrial proteins prohibitin 1 and cytochrome oxidase (COX) subunit IV also indicated that mitochondrial content was increased in TFEB‐DDK cells. (c) PGC‐1α mRNA levels were measured in SH‐SY5Y cells and TFEB‐DDK cells under basal conditions by qPCR. Data normalised against β‐actin mRNA levels. **p < 0.01 versus SH‐SY5Y cells; n = 3. (d) SH‐SY5Y cells were treated with scrambled (scram) or TFEB siRNA for 72 h and PGC‐1α mRNA levels measured. *p < 0.05 versus scram; n = 4. (e) PGC‐1α protein levels were detected by western blotting in total cell lysates of SH‐SY5Y cells, TFEB‐DDK cells and a SH‐SY5Y cell line over‐expressing human PGC‐1α. The fold increase in PGC‐1α protein density for this blot and PGC‐1α mRNA levels of the respective cell lines are reported underneath the blot. (f) TFEB‐DDK cells were treated with 10 μM carbonyl cyanide m‐chlorophenylhydrazone (CCCP) for 18 h and cytosolic and nuclear fractions prepared. PGC‐1α protein was detected in cytosolic (3.5% of total volume) and nuclear fractions (35% of total volume) by western blotting. The purity of the nuclear and cytosolic fractions was assessed by western blotting using lamin A and β‐actin antibodies respectively.CC BY · PubMed Central
Figure 8 Activation of Nrf2 and TFEB following mitophagy induction. Stimulation of PINK1‐dependent mitophagy results in the nuclear translocation of the transcription factors Nrf2 and TFEB. Both transcription factors increase the expression of the autophagic protein p62. Nrf2 is involved in the antioxidant response and mitochondrial biogenesis. TFEB also increases lysosomal biogenesis and can affect mitochondrial biogenesis by increasing expression of PGC‐1α. Activation of Nrf2 and TFEB following damage to mitochondria and induction of mitophagy will likely coordinate protection from oxidative stress (via antioxidant response element), replace damaged mitochondria removed by mitophagy, and maintain efficient macroautophagy by stimulating expression of autophagic proteins such as p62 and synthesis of lysosomal enzymes.
Figure 8 Activation of Nrf2 and TFEB following mitophagy induction. Stimulation of PINK1‐dependent mitophagy results in the nuclear translocation of the transcription factors Nrf2 and TFEB. Both transcription factors increase the expression of the autophagic protein p62. Nrf2 is involved in the antioxidant response and mitochondrial biogenesis. TFEB also increases lysosomal biogenesis and can affect mitochondrial biogenesis by increasing expression of PGC‐1α. Activation of Nrf2 and TFEB following damage to mitochondria and induction of mitophagy will likely coordinate protection from oxidative stress (via antioxidant response element), replace damaged mitochondria removed by mitophagy, and maintain efficient macroautophagy by stimulating expression of autophagic proteins such as p62 and synthesis of lysosomal enzymes.CC BY · PubMed Central

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Metadata

Authors
Ivankovic, D., Chau, K., Schapira, A. H. V., & Gegg, M. E.
Affiliations
UCL Queen Square Institute of Neurology (GB)
Corresponding author
Gegg, Matthew E.
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2015-11-24
Volume
136
Issue
2
Pages
388-402
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/jnc.13412
PMC
PMC4949652
OpenAlex
W1853148353
Cited by
264
References
62
Citations by year
2026: 22 · 2025: 31 · 2024: 28 · 2023: 30 · 2022: 33 · 2021: 28 · 2020: 24 · 2019: 24 · 2018: 16 · 2017: 18 · 2016: 9
FWCI
11.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neurochemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Medical Research Council (MR/M006646/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords
mitophagy, PINK1, Parkin, autophagy-lysosome pathway, mitochondrial biogenesis, lysosomal biogenesis, p62, Nrf2, TFEB, PGC-1α, alpha-synuclein, Parkinson's disease, glucocerebrosidase, cathepsin D, mitochondrial dysfunction, SH-SY5Y cells
MeSH terms
Sequestosome-1 Protein, Mitochondrial Precursor Protein Import Complex Proteins, PTEN-Induced Putative Kinase, Carbonyl Cyanide m-Chlorophenyl Hydrazone, Cell Nucleolus, Cytosol, Gene Expression Regulation, Heat-Shock Proteins, Humans, Lysosomes, Mitochondria, Neuroblastoma, Protein Kinases, Receptors, Cell Surface, Time Factors, Transfection, Tubulin, Gene Expression Regulation, Neoplastic, Membrane Transport Proteins, RNA, Small Interfering, Ubiquitin-Protein Ligases, Cell Line, Tumor, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Proton Ionophores, Mitophagy

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