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J Neurosci. 2015 Jun 24;35(25):9391-401. doi: 10.1523/JNEUROSCI.1198-15.2015.

The Organization of Mitochondrial Quality Control and Life Cycle in the Nervous System In Vivo in the Absence of PINK1.

Author information

1
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.
2
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907 phollenb@purdue.edu.

Abstract

Maintenance of healthy mitochondria is crucial in cells, such as neurons, with high metabolic demands, and dysfunctional mitochondria are thought to be selectively degraded. Studies of chemically uncoupled cells have implicated PINK1 mitochondrial kinase, and Parkin E3 ubiquitin ligase in targeting depolarized mitochondria for degradation. However, the role of the PINK1/Parkin pathway in mitochondrial turnover is unclear in the nervous system under normal physiological conditions, and we understand little about the changes that occur in the mitochondrial life cycle when turnover is disrupted. Here, we evaluated the nature, location, and regulation of quality control in vivo using quantitative measurements of mitochondria in Drosophila nervous system, with deletion and overexpression of genes in the PINK1/Parkin pathway. We tested the hypotheses that impairment of mitochondrial quality control via suppression of PINK1 function should produce failures of turnover, accumulation of senescent mitochondria in the axon, defects in mitochondrial traffic, and a significant shift in the mitochondrial fission-fusion steady state. Although mitochondrial membrane potential was diminished by PINK1 deletion, we did not observe the predicted increases in mitochondrial density or length in axons. Loss of PINK1 also produced specific, directionally balanced defects in mitochondrial transport, without altering the balance between stationary and moving mitochondria. Somatic mitochondrial morphology was also compromised. These results strongly circumscribe the possible mechanisms of PINK1 action in the mitochondrial life cycle and also raise the possibility that mitochondrial turnover events that occur in cultured embryonic axons might be restricted to the cell body in vivo, in the intact nervous system.

KEYWORDS:

Drosophila; PINK1; axonal transport; mitochondrial function; mitochondrial turnover; motor neurons

PMID:
26109662
PMCID:
PMC4478254
DOI:
10.1523/JNEUROSCI.1198-15.2015
[Indexed for MEDLINE]
Free PMC Article

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