Lysosomes in the Rat Sciatic Nerve Following Crush

Holtzman, Eric; Novikoff, Alex B.

doi:10.1083/jcb.27.3.651

Cited by 297 publications

(103 citation statements)

References 39 publications

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“…103 The scarcity of lysosomes in axons may suggest that mitochondrial degradation preferentially occurs in the soma. While it may take days for axonal transport to deliver an organelle to the soma for degradation, rapid elimination of dysfunctional mitochondria is probably critical for protection of neurons against oxidative damage and degeneration.…”

Section: Mitophagy In Neuronsmentioning

confidence: 99%

The pathways of mitophagy for quality control and clearance of mitochondria

2012

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Selective autophagy of mitochondria, known as mitophagy, is an important mitochondrial quality control mechanism that eliminates damaged mitochondria. Mitophagy also mediates removal of mitochondria from developing erythrocytes, and contributes to maternal inheritance of mitochondrial DNA through the elimination of sperm-derived mitochondria. Recent studies have identified specific regulators of mitophagy that ensure selective sequestration of mitochondria as cargo. In yeast, the mitochondrial outer membrane protein autophagy-related gene 32 (ATG32) recruits the autophagic machinery to mitochondria, while mammalian Nix is required for degradation of erythrocyte mitochondria. The elimination of damaged mitochondria in mammals is mediated by a pathway comprised of PTEN-induced putative protein kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin. PINK1 and Parkin accumulate on damaged mitochondria, promote their segregation from the mitochondrial network, and target these organelles for autophagic degradation in a process that requires Parkin-dependent ubiquitination of mitochondrial proteins. Here we will review recent advances in our understanding of the different pathways of mitophagy. In addition, we will discuss the relevance of these pathways in neurons where defects in mitophagy have been implicated in neurodegeneration. Facts Mitophagy mediates clearance of damaged mitochondria, and is also involved in the removal of mitochondria from maturing erythrocytes and eliminating sperm-derived mitochondria after fertilization. In yeast, the mitochondrial outer membrane protein autophagy-related gene 32 (ATG32) recruits the core autophagic machinery to mitochondria for their selective removal. A pathway containing PTEN-induced putative protein kinase 1 (PINK1) and Parkin responds to loss of mitochondrial membrane potential by targeting damaged mitochondria for clearance. The PINK1/Parkin pathway is triggered when PINK1 is stabilized on the outer membrane of damaged mitochondria, where it facilitates recruitment of cytosolic Parkin. Damaged mitochondria are prevented from moving and fusing with the mitochondrial reticulum in preparation for their mitophagic clearance. Open QuestionsHow distinct are the mitophagy pathways triggered by different stimuli or conditions?To what extent does Parkin activate mitophagy by causing the degradation of mitochondrial surface proteins or hyperubiquitinating the mitochondrial surface? How do PINK1 and Parkin interact with one another and with substrates on the mitochondrial surface in causing mitophagy? In contrast to the remarkable conservation of the core autophagic machinery, why are mitophagy-specific genes so little conserved between yeast and mammals? How best should mitophagy be triggered by researchers probing physiologically relevant pathways?The mitochondrion is an important actor in the life of a eukaryotic cell, but, like all good actors, a mitochondrion needs to exit the stage at the right time. Mitophagy removes mitochondria once they have played their part. This artic...

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Section: Mitophagy In Neuronsmentioning

confidence: 99%

The pathways of mitophagy for quality control and clearance of mitochondria

2012

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“…However, the removal process of the myelin sheath during Wallerian degeration is not completely clear and there is still considerable controversy as to the type of cells involved in the removal. Many investigators have suggested that only Schwann cells (9,12), or macrophages (4,6,17) or both cell types (5,13,15) participate in the removal of the myelin sheath during nerve degeneration. Some investigators (5,12,13,19) found that Schwann cells and macrophages contained myelin fragments, but the source of the myelin fragments within the Schwann cells is still uncertain.…”

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confidence: 99%

The role of Schwann cells and macrophages in the removal of myelin during Wallerian degeneration.

Han

Piao

Guo

et al. 1989

Acta Histochem. Cytochem.

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Axonal changes, in particular the breakdown and removal of the myelin sheath, were studied using morphological method and cytochemical technique in the sciatic nerves of rats following transection. The details of axonal loss were examined during the first few days after transection. Axonal degradation was immediately accompanied by the fragmentation of the myelin sheath. It was found that: (a) a part of the myelin sheath separated from Schwann cells and smashed into debris, then the myelin debris was phagocytosed and digested by macrophages at endoneurial space; the others, most of the myelin sheath, remained within Schwann cells until being digested; (b) both small debris of myelin sheath (SDMS) and large membrane-bound myelin debris (LMBMD) were found in Schwann cells; acid phosphatase (AcPase) activity was detected in SDMS earlier than in LMBMD; (c) macrophages were found in myelin sheath tubes; they participated in removing a part of degenerating axons. Observation confirmed that Schwann cells had no ability to actively phagocytose myelin, that the majority of myelin debris were removed by Schwann cells, and that the minority of them were dealt with by macrophages. The ability of Schwann cells to digest myelin debris suggested that Schwann cells play a crucial role in vivo in removing myelin debris and that the process of myelin debris in Schwann cells might be significant for their mitotic activity.

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“…As the mitochondria are unstained with FRAP [11], the reason for the mitochondrial FRAP-like reaction is not known. After peripheral nerve crush, degenerated axonal mitochondria exhibited precipitation of lead phosphate [10]. Several types of axon terminals showed FRAP reactivity: one type consists of small round, slender, dark sinuous and large scalloped terminals with packed clear synaptic vesicles, and the other consists of larger roundish terminals with less packed clear synaptic vesicles and many mitochondria.…”

Section: Discussionmentioning

confidence: 99%