Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis

Abstract

OBJECTIVES: Mitochondrial dysfunction has been reported in the central nervous system, hepatocytes and peripheral blood lymphocytes from patients with sporadic amyotrophic lateral sclerosis (SALS). However, the status of skin mitochondria has not been reported, in spite of the fact that SALS patients present skin abnormalities. The objective of the present study was to compare mitochondrial ultrastructural parameters in keratinocytes from patients with SALS and healthy controls. METHODS: Our study was based on the analysis of 112 skin mitochondria from 5 SALS patients and 99 organelles from 4 control subjects by electron microscopy. RESULTS: Computerized image analysis showed that mitochondrial major axis length, area and perimeter of the organelle were significantly smaller in SALS respect of healthy control subjects. Morphologically, SALS mitochondria presented cristolysis and breakage of the outer membrane. CONCLUSIONS: Mitochondrial dysfunction in the skin may possibly reflect changes occurring in mitochondria of the central nervous system. The analysis of mitochondrial morphology in this tissue may be of value to follow disease progression and, eventually, the effectiveness of current therapies for SALS.

Sporadic amyotrophic lateral sclerosis: new hypothesis regarding its etiology and pathogenesis suggests that astrocytes might be the primary target hosting a still unknown external agent

“…All these features are not limited to the motor neurons; similar changes were found in liver 16 and muscle 17 cells and in lymphocytes 18 of SALS patients. More recently, we have described similar mitochondrial changes in skin cells from these patients 19 . These observations suggest that the oxidative stress is not just a phenomenon constrained to the motor neurons, but a widespread disturbance afflicting quite different organs within the body.…”

Is amyotrophic lateral sclerosis a primary astrocytic disease?

“…A possible argument against the present hypothesis is that, in addition to the central nervous system, other tissues may be affected in ALS, as evidenced by their mitochondrial abnormalities [70]. This is true, but it can also be explained as an epiphenomenon resulting from the oxidative stress which accompanies the whole disease, or by the putative ALS misfolded protein being present in other structures [71,72].…”

Decreased ceramide underlies mitochondrial dysfunction in Charcot‐Marie‐Tooth 2F

“…It is currently unknown whether the genetic etiologies of CMT2 subtypes have distinct mechanisms or converge on a pathway that will offer common targets for treatment. Mitochondrial morphology also has been linked to other neurodegenerative diseases, including Parkinson's disease and ALS (28,(60)(61)(62). Enlarged, swollen mitochondria similarly produced dysfunctional changes in Ullrich congenital muscular dystrophy (63).…”