5,017
Views
42
CrossRef citations to date
0
Altmetric
Research Paper

The role of mitophagy in the regulation of mitochondrial energetic status in neurons

, , ORCID Icon, ORCID Icon & ORCID Icon
Pages 4182-4201 | Received 06 Nov 2020, Accepted 18 Mar 2021, Published online: 05 Apr 2021

References

  • Sheng ZH, Cai Q. Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat Rev Neurosci. 2012 Jan 5;13(2):77–93.
  • Cai Q, Tammineni P. Alterations in mitochondrial quality control in alzheimer’s disease. Front Cell Neurosci. 2016;10:24.
  • Cai Q, Tammineni P. Mitochondrial aspects of synaptic dysfunction in alzheimer’s disease. J Alzheimers Dis. 2017;57(4):1087–1103.
  • Chamberlain KA, Sheng ZH. Mechanisms for the maintenance and regulation of axonal energy supply. J Neurosci Res. 2019 Aug;97(8):897–913.
  • Nicholls DG, Budd SL. Mitochondria and neuronal survival. Physiol Rev. 2000 Jan;80(1):315–360.
  • Mishra P, Chan DC. Mitochondrial dynamics and inheritance during cell division, development and disease. Nat Rev Mol Cell Biol. 2014 Oct;15(10):634–646.
  • Lou G, Palikaras K, Lautrup S, et al. Mitophagy and Neuroprotection. Trends Mol Med. 2020 Jan;26(1):8–20.
  • Cai Q, Jeong YY. Mitophagy in alzheimer’s disease and other age-related neurodegenerative diseases. Cells. 2020. 8. 9(1):Jan.
  • Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006 Oct 19;443(7113):787–795.
  • Bose A, Beal MF. Mitochondrial dysfunction in parkinson’s disease. J Neurochem. 2016 Oct;139(Suppl 1):216–231.
  • Fivenson EM, Lautrup S, Sun N, et al. Mitophagy in neurodegeneration and aging. Neurochem Int. 2017;109:202–209.
  • Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011 Jan;12(1):9–14.
  • Pickles S, Vigie P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol. 2018 Feb 19;28(4):R170–R185.
  • Melser S, Lavie J, Benard G. Mitochondrial degradation and energy metabolism. Biochim Biophys Acta. 2015 Oct;1853(10Pt B):2812–2821.
  • Wallace DC. A mitochondrial bioenergetic etiology of disease. J Clin Invest. 2013 Apr;123(4):1405–1412.
  • Gibson GE, Shi Q. A mitocentric view of alzheimer’s disease suggests multi-faceted treatments. J Alzheimers Dis. 2010;20(Suppl 2):S591–607.
  • Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9):609–633.
  • Camandola S, Mattson MP. Brain metabolism in health, aging, and neurodegeneration. Embo J. 2017 Jun 1;36(11):1474–1492.
  • Reddy PH, Beal MF. Are mitochondria critical in the pathogenesis of alzheimer’s disease? Brain Res Brain Res Rev. 2005 Nov;49(3):618–632.
  • Reddy PH, Reddy TP, Manczak M, et al. Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases. Brain Res Rev. 2011 Jun 24;67(1–2):103–118.
  • Kerr JS, Adriaanse BA, Greig NH, et al. Mitophagy and alzheimer’s disease: cellular and molecular mechanisms. Trends Neurosci. 2017 Mar;40(3):151–166.
  • Moreira PI, Siedlak SL, Wang X, et al. Increased autophagic degradation of mitochondria in alzheimer disease. Autophagy. 2007 Nov-Dec;3(6):614–615.
  • Moreira PI, Siedlak SL, Wang X, et al. Autophagocytosis of mitochondria is prominent in alzheimer disease. J Neuropathol Exp Neurol. 2007 Jun;66(6):525–532.
  • Ye X, Sun X, Starovoytov V, et al. Parkin-mediated mitophagy in mutant hAPP neurons and alzheimer’s disease patient brains. Hum Mol Genet. 2015 May 15;24(10):2938–2951.
  • Han S, Jeong YY, Sheshadri P, et al. Mitophagy regulates integrity of mitochondria at synapses and is critical for synaptic maintenance. EMBO Rep. 2020;6:e201949801.
  • Han S, Jeong YY, Sheshadri P, et al. Mitophagy coordination with retrograde transport ensures the integrity of synaptic mitochondria. Autophagy. 2020 Oct 16;(10):1925–1927.
  • Fang EF, Hou Y, Palikaras K, et al. Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of alzheimer’s disease. Nat Neurosci. 2019 Mar;22(3):401–412.
  • Du F, Yu Q, Yan S, et al. PINK1 signalling rescues amyloid pathology and mitochondrial dysfunction in alzheimer’s disease. Brain. 2017 Dec 1;140(12):3233–3251.
  • Reitzer LJ, Wice BM, Kennell D. Evidence that glutamine, not sugar, is the major energy source for cultured Hela cells. J Biol Chem. 1979 Apr 25;254(8):2669–2676.
  • Rossignol R, Gilkerson R, Aggeler R, et al. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res. 2004 Feb 1;64(3):985–993.
  • Melser S, Chatelain EH, Lavie J, et al. Rheb regulates mitophagy induced by mitochondrial energetic status. Cell Metab. 2013 May 7;17(5):719–730.
  • Weinberg F, Hamanaka R, Wheaton WW, et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A. 2010 May 11;107(19):8788–8793.
  • Imamura H, Nhat KP, Togawa H, et al. Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15651–15656.
  • Tantama M, Martinez-Francois JR, Mongeon R, et al. Imaging energy status in live cells with a fluorescent biosensor of the intracellular ATP-to-ADP ratio. Nat Commun. 2013;4:2550.
  • Berg J, Hung YP, Yellen G. A genetically encoded fluorescent reporter of ATP:ADP ratio. Nat Methods. 2009 Feb;6(2):161–166.
  • Waypa GB, Marks JD, Guzy R, et al. Hypoxia triggers subcellular compartmental redox signaling in vascular smooth muscle cells. Circ Res. 2010 Feb 19;106(3):526–535.
  • Xie H, Guan J, Borrelli LA, et al. Mitochondrial alterations near amyloid plaques in an alzheimer’s disease mouse model. J Neurosci. 2013 Oct 23;33(43):17042–17051.
  • Cai Q, Zakaria HM, Simone A, et al. Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons. Curr Biol. 2012 Mar 20;22(6):545–552.
  • Wu Z, Puigserver P, Andersson U, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999 Jul 9;98(1):115–124.
  • Picca A, Lezza AM. Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: useful insights from aging and calorie restriction studies. Mitochondrion. 2015 Nov;25:67–75.
  • Uittenbogaard M, Brantner CA, Chiaramello A. Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells. Cell Death Dis. 2018 Mar 2;9(3):360.
  • Sivalingam K, Cirino TJ, McLaughlin JP, et al. HIV-Tat and cocaine impact brain energy metabolism: redox modification and mitochondrial biogenesis influence NRF transcription-mediated neurodegeneration. Mol Neurobiol. 2021 Feb;58(2):490–504.
  • Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in parkinson’s disease. Neuron. 2015 Jan 21;85(2):257–273.
  • Devireddy S, Liu A, Lampe T, et al. The organization of mitochondrial quality control and life cycle in the nervous system in vivo in the absence of PINK1. J Neurosci. 2015 Jun 24;35(25):9391–9401.
  • Sung H, Tandarich LC, Nguyen K, et al. Compartmentalized regulation of parkin-mediated mitochondrial quality control in the drosophila nervous system in vivo. J Neurosci. 2016 Jul 13;36(28):7375–7391.
  • Xie Y, Zhou B, Lin MY, et al. Endolysosomal deficits augment mitochondria pathology in spinal motor neurons of asymptomatic fals mice. Neuron. 2015 Jul 15;87(2):355–370.
  • Maday S, Holzbaur EL. Compartment-specific regulation of autophagy in primary neurons. J Neurosci. 2016 Jun 1;36(22):5933–5945.
  • Tammineni P, Jeong YY, Feng T, et al. Impaired axonal retrograde trafficking of the retromer complex augments lysosomal deficits in alzheimer’s disease neurons. Hum Mol Genet. 2017 Nov 15;26(22):4352–4366.
  • Cai Q, Lu L, Tian JH, et al. Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons. Neuron. 2010 Oct 06;68(1):73–86.
  • Cheng XT, Xie YX, Zhou B, et al. Characterization of LAMP1-labeled nondegradative lysosomal and endocytic compartments in neurons. J Cell Biol. 2018 Sep 3;217(9):3127–3139.
  • Lee JH, Rao MV, Yang DS, et al. Transgenic expression of a ratiometric autophagy probe specifically in neurons enables the interrogation of brain autophagy in vivo. Autophagy. 2019 Mar;15(3):543–557.
  • Chan NC, Salazar AM, Pham AH, et al. Broad activation of the ubiquitin-proteasome system by parkin is critical for mitophagy. Hum Mol Genet. 2011 May 1;20(9):1726–1737.
  • Yoshii SR, Kishi C, Ishihara N, et al. Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane. J Biol Chem. 2011 Jun 3;286(22):19630–19640.
  • Birsa N, Norkett R, Wauer T, et al. Lysine 27 ubiquitination of the mitochondrial transport protein miro is dependent on serine 65 of the parkin ubiquitin ligase. J Biol Chem. 2014 May 23;289(21):14569–14582.
  • Bingol B, Tea JS, Phu L, et al. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 2014 Jun 19;510(7505):370-+.
  • Liu S, Sawada T, Lee S, et al. Parkinson’s disease-associated kinase PINK1 regulates miro protein level and axonal transport of mitochondria. PLoS Genet. 2012;8(3):e1002537.
  • Wang X, Winter D, Ashrafi G, et al. PINK1 and Parkin target miro for phosphorylation and degradation to arrest mitochondrial motility. Cell. 2011 Nov 11;147(4):893–906.
  • Cai Q, Zakaria HM, Sheng ZH. Long time-lapse imaging reveals unique features of PARK2/Parkin-mediated mitophagy in mature cortical neurons. Autophagy. 2012 Jun;8(6):976–978.
  • Lin MY, Cheng XT, Tammineni P, et al. Releasing syntaphilin removes stressed mitochondria from axons independent of mitophagy under pathophysiological conditions. Neuron. 2017 May 03;94(3):595–610 e6.
  • Bingol B, Tea JS, Phu L, et al. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 2014 Jun 19;510(7505):370–375.
  • Katayama H, Kogure T, Mizushima N, et al. A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery. Chem Biol. 2011 Aug 26;18(8):1042–1052.
  • Chen J, Herrup K. Glutamine acts as a neuroprotectant against DNA damage, beta-amyloid and H2O2-induced stress. PLoS One. 2012;7(3):e33177.
  • Chen J, Chen Y, Vail G, et al. The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment. Mol Neurodegener. 2016 Aug 18;11(1):60.
  • Du H, Guo L, Yan S, et al. Early deficits in synaptic mitochondria in an alzheimer’s disease mouse model. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18670–18675.
  • Nagahara AH, Merrill DA, Coppola G, et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of alzheimer’s disease. Nat Med. 2009 Mar;15(3):331–337.
  • Nagahara AH, Mateling M, Kovacs I, et al. Early BDNF treatment ameliorates cell loss in the entorhinal cortex of APP transgenic mice. J Neurosci. 2013 Sep 25;33(39):15596–15602.
  • Mucke L, Masliah E, Yu GQ, et al. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci. 2000 Jun 1;20(11):4050–4058.
  • Ye X, Feng T, Tammineni P, et al. Regulation of synaptic amyloid-beta generation through BACE1 retrograde transport in a mouse model of alzheimer’s disease. J Neurosci. 2017 Mar 08;37(10):2639–2655.
  • Hirai K, Aliev G, Nunomura A, et al. Mitochondrial abnormalities in alzheimer’s disease. J Neurosci. 2001 May 1;21(9):3017–3023.
  • Cai Q, Sheng ZH. Uncovering the role of snapin in regulating autophagy-lysosomal function. Autophagy. 2011 Apr;7(4):445–447.
  • Polito VA, Li H, Martini-Stoica H, et al. Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol Med. 2014 Sep;6(9):1142–1160.
  • Xiao Q, Yan P, Ma X, et al. Neuronal-targeted TFEB accelerates lysosomal degradation of APP, reducing abeta generation and amyloid plaque pathogenesis. J Neurosci. 2015 Sep 2;35(35):12137–12151.
  • Banerjee K, Munshi S, Frank DE, et al. Abnormal glucose metabolism in alzheimer’s disease: relation to autophagy/mitophagy and therapeutic approaches. Neurochem Res. 2015 Dec;40(12):2557–2569.
  • Neth BJ, Craft S. Insulin resistance and alzheimer’s disease: bioenergetic linkages. Front Aging Neurosci. 2017;9:345.
  • Sorrentino V, Menzies KJ, Auwerx J. Repairing mitochondrial dysfunction in disease. Annu Rev Pharmacol Toxicol. 2018 Jan;6(58):353–389.
  • Sorrentino V, Romani M, Mouchiroud L, et al. Enhancing mitochondrial proteostasis reduces amyloid-beta proteotoxicity. Nature. 2017 Dec 14;552(7684):187–193.
  • Lee S, Sato Y, Nixon RA. Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an alzheimer’s-like axonal dystrophy. J Neurosci. 2011 May 25;31(21):7817–7830.
  • Maday S, Wallace KE, Holzbaur EL. Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons. J Cell Biol. 2012 Feb 20;196(4):407–417.
  • Sepuri NBV, Tammineni P, Mohammed F, et al. Nuclear transcription factors in the mitochondria: a new paradigm in fine-tuning mitochondrial metabolism. Handb Exp Pharmacol. 2017;240:3–20.
  • Cheng XT, Xie YX, Zhou B, et al. Characterization of LAMP1-labeled nondegradative lysosomal and endocytic compartments in neurons. J Cell Biol. 2018 Sep 3;217(9):3127–3139.
  • Yap CC, Digilio L, McMahon LP, et al. Degradation of dendritic cargos requires Rab7-dependent transport to somatic lysosomes. J Cell Biol. 2018 Sep 3;217(9):3141–3159.
  • Gowrishankar S, Yuan P, Wu Y, et al. Massive accumulation of luminal protease-deficient axonal lysosomes at alzheimer’s disease amyloid plaques. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):E3699–708.
  • Overly CC, Lee KD, Berthiaume E, et al. Quantitative measurement of intraorganelle pH in the endosomal-lysosomal pathway in neurons by using ratiometric imaging with pyranine. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3156–3160.
  • Smith MA, Perry G, Richey PL, et al. Oxidative damage in alzheimer’s. Nature. 1996 Jul 11;382(6587):120–121.
  • Maurer I, Zierz S, Moller HJ. A selective defect of cytochrome c oxidase is present in brain of alzheimer disease patients. Neurobiol Aging. 2000 May-Jun;21(3):455–462.
  • Devi L, Prabhu BM, Galati DF, et al. Accumulation of amyloid precursor protein in the mitochondrial import channels of human alzheimer’s disease brain is associated with mitochondrial dysfunction. J Neurosci. 2006 Aug 30;26(35):9057–9068.
  • Caspersen C, Wang N, Yao J, et al. Mitochondrial abeta: a potential focal point for neuronal metabolic dysfunction in alzheimer’s disease. Faseb J. 2005 Dec;19(14):2040–2041.
  • Manczak M, Park BS, Jung Y, et al. Differential expression of oxidative phosphorylation genes in patients with alzheimer’s disease: implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med. 2004;5(2):147–162.
  • Manczak M, Calkins MJ, Reddy PH. Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with alzheimer’s disease: implications for neuronal damage. Hum Mol Genet. 2011 Jul 1;20(13):2495–2509.
  • Parker WD Jr., Filley CM, Parks JK. Cytochrome oxidase deficiency in alzheimer’s disease. Neurology. 1990 Aug;40(8):1302–1303.
  • Butterfield DA, Drake J, Pocernich C, et al. Evidence of oxidative damage in alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med. 2001 Dec;7(12):548–554.
  • Lin MT, Simon DK, Ahn CH, et al. High aggregate burden of somatic mtDNA point mutations in aging and alzheimer’s disease brain. Hum Mol Genet. 2002 Jan 15;11(2):133–145.
  • Coskun PE, Beal MF, Wallace DC. Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10726–10731.
  • Tonnies E, Trushina E. Oxidative stress, synaptic dysfunction, and alzheimer’s disease. J Alzheimers Dis. 2017;57(4):1105–1121.
  • Flannery PJ, Trushina E. Mitochondrial dynamics and transport in alzheimer’s disease. Mol Cell Neurosci. 2019 Jul;98:109–120.
  • Oliver DMA, Reddy PH. Molecular basis of alzheimer’s disease: focus on mitochondria. J Alzheimers Dis. 2019;72(s1):S95–S116.
  • Wang W, Zhao F, Ma X, et al. Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Mol Neurodegener. 2020 May 29;15(1):30.
  • Santos RX, Correia SC, Wang X, et al. Alzheimer’s disease: diverse aspects of mitochondrial malfunctioning. Int J Clin Exp Pathol. 2010 Jun 25;3(6):570–581.
  • Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. 2013 Aug;19(8):983–997.
  • Menzies FM, Fleming A, Rubinsztein DC. Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci. 2015 Jun;16(6):345–357.
  • Winckler B, Faundez V, Maday S, et al. The endolysosomal system and proteostasis: from development to degeneration. J Neurosci. 2018 Oct 31;38(44):9364–9374.
  • Puri R, Cheng XT, Lin MY, et al. Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts. Nat Commun. 2019 Aug 13;10(1):3645.
  • Ye X, Cai Q. Snapin-mediated BACE1 retrograde transport is essential for its degradation in lysosomes and regulation of APP processing in neurons. Cell Rep. 2014 Jan 16;6(1):24–31.
  • Banker GA, Cowan WM. Further observations on hippocampal neurons in dispersed cell culture. J Comp Neurol. 1979 Oct 1;187(3):469–493.
  • Kang JS, Tian JH, Pan PY, et al. Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation. Cell. 2008 Jan 11;132(1):137–148.
  • Frezza C, Cipolat S, Scorrano L. Organelle isolation: functional mitochondria from mouse liver, muscle and cultured fibroblasts. Nat Protoc. 2007;2(2):287–295.
  • Djordjevic J, Thomson E, Chowdhury SR, et al. Brain region- and sex-specific alterations in mitochondrial function and NF-kappaB signaling in the TgCRND8 mouse model of alzheimer’s disease. Neuroscience. 2017 Oct 11;361:81–92.
  • Hill BG, Dranka BP, Zou L, et al. Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem J. 2009 Oct 23;424(1):99–107.
  • Brand MD, Nicholls DG. Assessing mitochondrial dysfunction in cells. Biochem J. 2011 Apr 15;435(2):297–312.
  • Trushina E, Nemutlu E, Zhang S, et al. Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial alzheimer’s disease. PLoS One. 2012;7(2):e32737.
  • Nixon RA, Wegiel J, Kumar A, et al. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol. 2005 Feb;64(2):113–122.
  • Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1–222.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.